While scrounging around the latest smear campaign fall-out, I came across this article. I was shocked! Truly, something that made clear and concise sense. I imagine the article has been noted by others here, but for me, what a sweet aroma. God is being nice to me, with the plethora of deep devil doo-doo that I am wading through.
You are so right, when they say novel, that means created one. ABG1, a Novel and Essential Candida albicans Gene Encoding a Vacuolar Protein Involved in Cytokinesis and Hyphal Branching
Putative: 'putative' means 'supposed to exist' - so a putative gene is a gene that you think exists but have no direct evidence for. For example, you may have identified a phenotype that appears to depend on a single gene - but the gene has not yet been identified. answers.yahoo.com/question/index?qid=20081009025528AAC9qlx
Immunoscreening of a Candida albicans expression library resulted in the isolation of a novel gene encoding a 32.9-kDa polypeptide (288 amino acids), with 27.7% homology to the product of Saccharomyces cerevisiae YGR106c, a putative vacuolar protein. Heterozygous mutants in this gene displayed an altered budding growth pattern, characterized by the formation of chains of buds, decreasingly in size towards the apex, without separation of the daughter buds. Consequently, this gene was designated ABG1. A conditional mutant for ABG1 with the remaining allele under the control of the MET3 promoter did not grow in the presence of methionine and cysteine, demonstrating that ABG1 was essential for viability.
Western analysis revealed the presence of a major 32.9-kDa band, mainly in a particulate fraction (P40) enriched in vacuoles, and tagging with green fluorescent protein confirmed that Abg1p localized to the vacuole. Vacuole inheritance has been linked to the regulation of branching frequency in C. albicans. Under repressing conditions, the conditional mutant had an increased frequency of branching under hyphal inducing conditions and an altered sensitivity to substances that interfered with cell wall assembly. Repression of ABG1 in the conditional mutant strain caused disturbance of normal size and number of vacuoles both in yeast and mycelial cells and also in the asymmetric vacuole inheritance associated with the characteristic pattern of germ tubes and branching in C. albicans. These observations indicate that ABG1 plays a key role in vacuole biogenesis, cytokinesis, and hyphal branching.
FIG. 6. Phase-contrast microscopy observations of CAI4-URA3 (A, B, and C) and CV3 (D, E, F, and G) incubated under conditions to induce hyphal growth (see Materials and Methods). Bar = 10 µm in all panels. Arrows in panels D, E, F, and G point to branches in hyphal filaments.
FIG. 8. Vacuole morphology in hyphal cells. Phase-contrast (A, C, and E) and FM4-64-staining fluorescence observations (B, D, and F) of CAI4-URA3 (A and B) and CV3 (C-F) strains. ABG1 conditional mutant cells had several small vacuoles in each cellular compartment (D, F), while in the wild-type cells a single, large vacuole that occupied almost all the cytoplasmic volume was observed (B). Bar = 10 µm in all panels.
Polarisome Meets Spitzenkörper: Microscopy, Genetics, and Genomics Converge
The impact of filamentous fungi on human welfare has never been greater. Fungi are acknowledged as the most economically devastating plant pathogens (1) and are attaining increasing notoriety for their ability to cause life-threatening infections in humans (57, 71), and fungal products sustain a billion-dollar manufacturing industry (70). The tools available to study filamentous fungi are more sophisticated than ever and include the complete annotated genome sequences of multiple filamentous fungi (12), resources being made available through various functional genomics projects, and advanced bioimaging methods, including high-resolution live-cell imaging (20, 32) and electron tomography (19, 50). The increasing impact of filamentous fungi, along with the rediscovery of pseudohyphal growth in yeast (22), has focused attention on the molecular mechanisms underlying hyphal morphogenesis. Attempts to understand hyphal morphogenesis have historically followed two different lines of investigation. Microscopists have defined, with increasing detail, the subcellular organization of the hyphal tip. This led to the description of the Spitzenkörper, an apical cluster of vesicles, cytoskeletal elements, and other proteins, which plays a crucial role in hyphal extension (4). Geneticists have identified gene products required for hyphal morphogenesis by characterizing morphological mutants (51, 52). Initial studies in the laboratories of Beadle, Tatum, and colleagues attempted to link morphogenesis to specific biochemical pathways. More recent screens have identified a multitude of signaling and cytoskeletal functions required for hyphal extension (62, 72).
Candida albicans is termed a dimorphic fungus because it proliferates in either a yeast form or a hyphal form. The switch between these forms is the result of a complex interplay of external and internal factors and is coordinated in part by polarity-regulating proteins that are conserved among eukaryotic cells. However, yeast and hyphal cells are not the only morphological states of C. albicans. The opaque form required for mating, the pseudohyphal cell, and the chlamydospore represent distinct cell types that form in response to specific genetic or environmental conditions. In addition, hyperextended buds can form as a result of various cell cycle–related stresses. Recent studies are beginning to shed light on some of the molecular controls regulating the various morphogenetic forms of this fascinating human pathogen.
ties into our cytoskeletal cells, includes, blood cells
Candida albicans Rho-Type GTPase-Encoding Genes Required for Polarized Cell Growth and Cell Separation
There is a strong interest in studying the molecular basis of cell differentiation in Candida albicans based on the importance of the yeast-to-hypha transition as a virulence trait in this human fungal pathogen (5). Upon induction by environmental cues, C. albicans produces hyphal filaments that enable C. albicans to adhere to and penetrate tissues and thus conquer new territories or niches in the human host or escape from the host's cellular immune defense.
In the fungal realm this is what we are dealing with>
C. albicans is a human fungal pathogen that changes growth forms in response to environmental stimuli or host niches (5). Based on the yeast paradigm of polarized cell growth, a number of molecular analyses in recent years have identified GTP-binding proteins as being key regulators of polarized cell growth and/or hyphal morphogenesis in a variety of fungal species including, for example, A. gossypii, C. albicans, Ustilago maydis, and S. pombe
Candida albicans hyphae have a Spitzenkörper that is distinct from the polarisome found in yeast and pseudohyphae
In the budding yeast Saccharomyces cerevisiae, polarised growth is mediated by the polarisome, a surface cap of proteins that nucleates the formation of actin cables delivering secretory vesicles to the growing tip. The human fungal pathogen, Candida albicans, can grow in all three morphological forms. Here we show the presence of a Spitzenkörper at the tip of C. albicans hyphae as a ball-like localisation of secretory vesicles, together with the formin Bni1 and Mlc1, an ortholog of an S. cerevisiae myosin regulatory light chain
These results, together with the cytological differences between the cell types, suggest that the Spitzenkörper and polarisome are distinct structures, that the polarisome and Spitzenkörper coexist in hyphae, and that polarised growth in hyphae is driven by a fundamentally different mechanism to that in yeast and pseudohyphae. Key words * Hyphae * Actin cables * Microtubules * BUD6 * MLC1 * FM4-64 * Pseudohyphae * SPA2
The human fungal pathogen C. albicans can grow in yeast, pseudohyphal and hyphal growth forms: a property that is thought to be important for its virulence. It thus provides the opportunity to compare, in the same organism, the mechanisms of polarised growth operating in these different growth forms.
Fig. 2. Localisation of Bni1-YFP, Spa2-YFP and Bud6-GFP. (A) The fluorescence from Bni1-YFP merged with the DIC image of a germ tube. A single spot is observed just behind the tip (arrow). (B) Z-stack projection of hyphal cells expressing Spa2-YFP, which can be seen in all cells to form crescents or caps, with areas of higher intensity staining. (C) Localisation of Bud6-GFP, which predominantly forms a crescent, although in some cells a spot of higher fluorescence is observed (arrow). (D) Partial colocalisation of Spa2-YFP and Mlc1-CFP in hyphal cells. (E) Partial colocalisation of Spa2-YFP and FM4-64 in hyphal cells. Arrow indicates the tip that is enlarged in the model below. The model was constructed using the model-building module in the Softworx™ suite. Spa2-YFP is shown as a green wireframe, FM4-64 is shown in solid red. The Spa2 cap covers the solid body of FM4-64. Bar, 5 μm (A); 1 μm (B,E); 2 μm (C,D).
========= aspergillus nidulins, another aspergillus fumigatus has been found and determined in specimens from Morg person.
FIG. 4. Deletion of GapA affects conidiophore development. (A) Wild-type conidiophore. v, vesicle; m, metullae; p, phialides; c, conidia. (B) Mutant conidiophore. (C) Mutant conidiospore where conidia arise from primary sterigmata (white arrowheads). A normal primary sterigmata is not discernible in the spore chain indicated with a white star. c, conidia. (D) Mutant conidiospore showing several abnormally round-shaped metullae (white stars) and an ellipsoid one (white arrow). Bars, 10 µm.
Ras is found in the RHO A and cdc42.......... in Cytoskeletal restructuring.
======== Cdc42: An Essential Rho-Type GTPase Controlling Eukaryotic Cell Polarity
including human EUKAROTIC CELLS..................
Cdc42: An Essential Rho-Type GTPase Controlling Eukaryotic Cell Polarity
In addition, Cdc42p has been implicated in a number of human diseases through interactions with its regulators and downstream effectors. While much is known about Cdc42p sturcture and functional interactions, little is known about the mechanism(s) by which it transduces signals within the cell. Future research sould focus on this question as well as on the detailed analysis of the interactions of Cdc42p with its regulators and downstream effectors.
=========== DNA and predicted amino acid sequence analysis (242) indicated that Cdc42p belongs to the Rho subfamily of the Ras superfamily of GTPases that act as molecular switches in the control of a variety of eukaryotic processes (191, 239, 241, 242, 642) (see below). At about the same time, a ~25-kDa guanine nucleotide binding protein was purified from bovine brain and human placental membranes (140, 461, 582), and peptide sequences from this protein, termed Gp or G25K, showed a high degree of similarity to S. cerevisiae Cdc42p (242, 461). This protein was shown to be a good in vitro substrate for epidermal growth factor (EGF)-stimulated phosphorylation (209), although the in vivo phosphorylation of Cdc42p has not been reported to date. Subsequent analysis of the predicted amino acid sequence from two independent human cDNA isolates indicated the existence of two highly conserved (95% identical) proteins, the ubiquitously expressed Cdc42Hs (525) and the brain isoform G25K (407). The Cdc42Hs and G25K proteins are identical in both nucleotide and predicted amino acid sequences up to amino acid 163 but diverge from residues 163 to 191, suggesting that these isoforms are differential splicing products of a single gene.
Structural and/or functional Cdc42p homologs have subsequently been characterized in the pathogenic yeast Candida albicans (394), S. pombe (390), C. elegans (88, 500), Drosophila (336), chicken (Gallus gallus) cochlea (172), mouse (Mus musculus) liver (172) and brain (367), and dog (Canus familiaris) (GenBank accession no. Z49944), and these homologs are 80 to 95% identical in predicted amino acid sequence (241) (see below) (Fig. 1). S. pombe, Drosophila, and C. elegans Cdc42p, as well as Cdc42Hs and G25K, can complement the cdc42-1ts mutant (88, 390, 407, 507, 525), suggesting that Cdc42p may have conserved functions in these other eukaryotes.
FIG. 4. Comparison of Cdc42 interactions and dependent processes in S. cerevisiae (A), S. pombe (B), and mammals (C). Color and shape coding is given in the box at the bottom of figure. Two-headed arrows indicate physical interactions. Single-headed arrows indicate pathways; dotted arrows indicate potential involvement in pathways. For simplicity, not all components of the actin cytoskeleton or JNK kinase cascade are shown. See the text for details.
Mammalian Cdc42p has been implicated in a wide variety of in vivo functions including receptor-mediated signal transduction pathways leading to induction of transcription and actin rearrangements, cell cycle progression, and apoptosis. Most of these studies have relied on the phenotypic analysis of ectopic expression of dominant activated and dominant negative cdc42 mutants. In addition, the characterization of mammalian Cdc42p-interacting proteins has implicated Cdc42p in multiple pathways (Fig. 4C), whose regulation is still unclear.
As detailed in the above sections, the analysis of Cdc42p function in cultured mammalian cells and the characterization of Cdc42p effectors and regulators suggest that Cdc42p functions in a variety of human diseases through modulation of the actin cytoskeleton and JNK-dependent transcriptional induction events
(see above for references).
First, the observations that (i) Cdc42p is implicated in Ras-dependent cellular transformation, (ii) injection of Cdc42G12V-expressing cells into athymic nude mice led to the formation of tumors, and (iii) expression of the Cdc42F28L mutant protein led to cellular transformation similar to that seen with expression of the dbl oncogene (a Cdc42p GEF)
indicate that activation of Cdc42p can lead to malignant transformation and that cdc42 is a bona fide oncogene.It should be noted, however, that the presence of activated Cdc42 alleles in human tumor cells has not been reported to date.
Second, the mammalian WAS proteins, encoded by the genetic locus responsible for the Wiskott-Aldrich syndrome immunological disorder, bind specifically to GTP-Cdc42p, but not to GTP-bound RhoA or Rac1, and mediate Cdc42p-actin interactions.
Third, the polycystic kidney disease I (PKD1) protein, which plays a role in autosomal dominant polycystic kidney disease, was shown to induce c-Jun/AP-1 transcriptional activation through the activation of the Cdc42-dependent JNK pathway.
Fourth, the myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) interacts with Cdc42p in the regulation of actin rearrangements.
Fifth, the faciogenital dysplasia protein FGD1, which is encoded by the genetic locus responsible for the X-linked developmental disorder Aarskog-Scott syndrome, is believed to be a Cdc42-specific GEF in vivo.
Sixth, activation of the Nef-associated kinase (NAK) was mediated through Cdc42p, suggesting that Cdc42p plays a role in Nef-dependent HIV replication.
Finally, the Salmonella SopE protein acts as a GEF for Cdc42p, leading to the actin rearrangements necessary for Salmonella invasion of host epithelial cells. It is likely that Cdc42p will also play a critical role in other human diseases that involve actin rearrangements or JNK pathway activation,
and so a detailed understanding of Cdc42p structure and function could be invaluable in developing therapeutic strategies.
CONCLUSIONS AND FUTURE RESEARCH DIRECTIONS
The experimental results detailed in this review strongly support a model in which Cdc42p interacts with multiple regulators and effectors to activate a variety of cellular processes. It is interesting that Cdc42p has not been implicated as a negative or inhibitory factor in any cellular process; therefore, its roles seem to be positive or stimulatory in nature. The two primary Cdc42-dependent pathways leading to actin rearrangements and transcriptional inductions through protein kinase signaling cascades seem to be conserved in most cell types examined.
However, it is dangerous to extrapolate precise Cdc42p functions or mutational phenotypes from one organism to another, given, for instance, the differences in phenotypes seen between analogous cdc42 mutants in S. cerevisiae and S. pombe (see "Functional studies" above). It has been difficult to address whether the downstream effectors that mediate these two pathways are separate and independent or whether there is substantial cross-talk between the physiological pathways. This question should be vigorously addressed in the future.
It is unfortunate that despite all the detailed information we have garnered about Cdc42 functions and interacting proteins, we have little experimental data addressing the specific mechanism(s)-of-action for Cdc42p in these different cellular processes. It seems likely that one of the major roles that Cdc42p plays is in transducing exogenous and/or endogenous signals to downstream effectors by specifically binding and localizing these effectors to the appropriate subcellular locations so that they can interact with further downstream components, in much the same manner that Ras does with Raf.
The formation of these multiprotein complexes at discrete locations within the cell in response to different signals could be a primary regulatory mechanism for the specificity of Cdc42p function within different pathways. This hypothesis should be tested in the future through the phenotypic analysis of different Cdc42p effector domain mutations and their interactions with different downstream effectors and through subcellular colocalization studies with epitope-tagged or GFP fusion proteins
. The observations that Cdc42p can function at several points in the cell cycle adds an additional layer of complexity to understanding these differential regulatory interactions, but analysis of different effector domain mutations should provide some insight into this aspect of Cdc42p function as well.
So what are the future research directions for deciphering Cdc42p function? The answer to this question will be determined partly by the organism in which experiments are performed. For instance, genetic and biochemical studies in S. cerevisiae and in cultured mammalian cells, and to a lesser extent in S. pombe, have identified a myriad of Cdc42p regulators and effectors, but only recently have experiments designed to test specific protein-protein interactions and multiprotein complex formation been performed.
In addition, little is known about the in vivo specificity of assorted GEFs, GAPs, GDIs, or downstream effectors or about the targeting mechanisms for Cdc42p to the plasma membrane at sites of polarized growth in response to different signals or at different times in the cell cycle.
Therefore, future experiments with these organisms will probably focus on these issues. Few Cdc42p effectors and regulators have been identified or characterized in Drosophila and C. elegans, and so these proteins must be isolated before detailed mechanistic questions can be addressed.
However, the mechanistic studies in yeast and mammalian cells should develop useful paradigms that will allow for more defined questions to be addressed in Drosophila and C. elegans.
Interestingly, no bona fide Cdc42p homologs have been identified in fungal systems outside of the unicellular yeast or in plant systems, although multiple Rac homologs have been identified (118, 319, 563, 598). Given the high degree of cellular polarization seen in fungal and plant cell growth patterns, it would be surprising if Cdc42p homologs did not exist and were not involved in these processes.
Finally, given the recent determination of the NMR and X-ray crystal structures of Cdc42p and Cdc42p complexed with one of its GAPs, future molecular modeling studies could provide valuable insight into the effects of various loss-of-function, gain-of-function, and effector domain mutations on Cdc42p structure and function and its interactions with downstream effectors and regulators. The much anticipated NMR and/or X-ray crystal structure determinations of Cdc42p complexed with a downstream effector or GEF or GDI should greatly enhance our knowledge of the mechanisms of action of these proteins. All in all, the explosion of research centered on Cdc42p over the past 5 to 10 years has only served to whet our appetite for more details, which will certainly be forthcoming in the very near future.
Isoprene (short for isoterpene), or 2-methyl-1,3-butadiene, is a common organic compound with the formula CH2=C(CH3)CH=CH2. Under standard conditions it is a colorless liquid. However, this compound is highly volatile because of its low boiling point.
Isoprene (C5H8) is the monomer of natural rubber and also a common structure motif to an immense variety of other naturally occurring compounds, collectively termed the isoprenoids. Molecular formula of isoprenoids are multiples of isoprene in the form of (C5H8)n, and this is termed the isoprene rule. The functional isoprene units in biological systems are dimethylallyl diphosphate (DMADP) and its isomer isopentenyl diphosphate (IDP).
The singular terms “isoprene” and “terpene” are synonymous whereas the plurals “isoprenes” or “terpenes” refer to terpenoids (isoprenoids).
======================= I am on a roll, folks,,,,,,,,,,,hang on.....................
The isoprenoid moiety of cell signaling proteins. An emerging drug target in multiple diseases
During the last twenty years much effort has been invested in deciphering the intricate network of pathways that give support to the communication between cells and their environment. Two types of structurally different GTP binding proteins, monomeric and trimeric, play a central role for multiple signaling cascades. Trimeric GTP-binding proteins are composed by three subunits, α, β, and γ, and functionally couple the G- protein-linked receptors to their target enzymes or ion channels. Monomeric GTP-binding proteins comprise the superfamily of Ras-related-proteins, that provide crucial links in the intracellular signaling cascades activated by growth factors. This superfamily of proteins includes the small GTPases Ras, Rho, Rab, Rac, and others. Many of these proteins are involved in signaling pathways that regulate cell replication and differentiation, cytoskeletal organization, and vesicular trafficking(1) .
repeating: This superfamily of proteins includes the small GTPases Ras, Rho, Rab, Rac, and others. Many of these proteins are involved in signaling pathways that regulate cell replication and differentiation, cytoskeletal organization, and vesicular trafficking(1)d"
Ah yes, from the hidden Jena science community. who knows what they have achieved>
GTPases of the Ras superfamily represent a group of more than fifty proteins that function as molecular switches controlling a variety of signaling and transport pathways essential for numerous cellular functions. They were grouped, according to sequence homologies, into five principal branches: Ras family, Rab family, Ran family, Rho/Rac/Cdc42 family and Sar1/Arf family.
While mutations in Ras proteins are found in 30 to 60% of human malignancies, other GTPases like Rho and Rac have also been linked to oncogenesis.
Make sure you also check out our GTPase Activation Kits, providing rapid, cost-effective and reliable tools for the detection and semi-quantitative analysis of the cellular activation state of several GTPases!
so clicked number got this RIGHT AT CHROMOSOME 1, 1q42q.............
CDC42BPA CDC42 binding protein kinase alpha (DMPK-like) [ Homo sapiens ] Gene ID: 8476, updated on 17-May-2011
Official Symbol CDC42BPAprovided by HGNC Official Full Name CDC42 binding protein kinase alpha (DMPK-like)provided by HGNC Primary source HGNC:1737 Locus tag RP5-1087E8.4 See related Ensembl:ENSG00000143776; HPRD:04562; MIM:603412 Gene type protein coding RefSeq status REVIEWED Organism Homo sapiens Lineage Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo Also known as MRCK; MRCKA; PK428; FLJ23347; KIAA0451; DKFZp686L1738; DKFZp686P1738; CDC42BPA Summary The protein encoded by this gene is a member of the Serine/Threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described, and the full-length nature of two of them has been reported.
chromosome: 1; Location: 1q42.1
Related articles in PubMed
1. A human MAP kinase interactome. Bandyopadhyay S, et al. Nat Methods, 2010 Oct. PMID 20936779. 2. Human MRCKalpha is regulated by cellular iron levels and interferes with transferrin iron uptake. Cmejla R, et al. Biochem Biophys Res Commun, 2010 Apr 30. PMID 20188707. 3. Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta. Choi SH, et al. J Biol Chem, 2008 Apr 18. PMID 18263588. 4. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases. Lefort K, et al. Genes Dev, 2007 Mar 1. PMID 17344417. 5. The DNA sequence and biological annotation of human chromosome 1. Gregory SG, et al. Nature, 2006 May 18. PMID 16710414.
See all (24) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene
======================== So were terpenoids added? Yes, it the isoprenylation was there. Glue to bind to extracellular matrix. =====================
. Sometimes terpenoids are added to proteins, e.g., to enhance their attachment to the cell membrane; this is known as isoprenylation.
There are two metabolic pathways of creating terpenoids: Mevalonic acid pathway
Many organisms manufacture terpenoids through the HMG-CoA reductase pathway, the pathway that also produces cholesterol. The reactions take place in the cytosol. The pathway was discovered in the 1950s. MEP/DOXP pathway
The 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway (MEP/DOXP pathway), also known as [non-mevalonate pathway] or mevalonic acid-independent pathway, takes place in the plastids of plants and apicomplexan protozoa, as well as in many bacteria. It was discovered in the late 1980s.
CDC42BPA human: CDC42 binding protein kinase alpha (DMPK-like) Aliases: CDC42-binding protein kinase alpha, ser-thr protein kinase PK428, CDC42 binidng protein kinase beta, CDC42-binding protein kinase alpha (DMPK-like), myotonic dystrophy kinase-related CDC42-binding protein kinase alpha, ser-thr protein kinase related to the myotonic dystrophy protein kinase, MRCK, CDC42BPA, MRCKA, PK428, FLJ23347, KIAA0451, DKFZp686L1738, DKFZp686P1738
Pfam Domain Structure pfam domain structure for Q5VT25 Protein Overview Official Gene Name CDC42BPA (H. sapiens) RefSeq Protein Name CDC42 binding protein kinase alpha (DMPK-like) UniProt Gene Symbol MRCKA_HUMAN UniProt Name Serine/threonine-protein kinase MRCK alpha Entrez Gene Summary The protein encoded by this gene is a member of the Serine/Threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described, and the full-length nature of two of them has been reported. [provided by RefSeq]
1. Lefort K, Mandinova A, Ostano P, Kolev V, Calpini V, Kolfschoten I, Devgan V, Lieb J, Raffoul W, Hohl D, Neel V, Garlick J, Chiorino G, Dotto GP. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases Genes Dev. 2007 21:562-77 (PubMed) 2. Wilkinson S, Paterson HF, Marshall CJ. Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion Nat. Cell Biol. 2005 7:255-61 (PubMed) 3. Yamashiro S, Totsukawa G, Yamakita Y, Sasaki Y, Madaule P, Ishizaki T, Narumiya S, Matsumura F. Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II Mol. Biol. Cell 2003 14:1745-56 (PubMed) 4. Zhao ZS, Manser E. PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation Biochem. J. 2005 386:201-14 (PubMed) Consortium Results & Data Discovery» siRNA migration screen using a wound healing approach Gene Description MCF-10A phenotype Secondary screen Wound Image Morphology Time-lapse CDC42BPA Aliases: MRCK, MRCKA, PK428 Entrez Gene: 8476 siRNA catalog CDC42 binding protein kinase alpha (DMPK-like) mRNA: NM_003607 Library: Kinase Classification: Ser/Thr Kinase;Tyr Kinase Final bin: Discordant SMARTpool bin: No change Avg area: 1.40 Avg Alamar: 1.03 Knockdown %: 60-70 CDC42BPA Link CDC42BPA Link Discovery» siRNA Focal Adhesion Phenotypes Gene Description High-Res Montage CDC42BPA Aliases: MRCK, MRCKA, PK428 Entrez Gene: 8476 siRNA catalog CDC42 binding protein kinase alpha (DMPK-like) mRNA: NM_003607 Library: Kinase CDC42BPA Link CDC42BPA Link Discovery» wt-migratory_cells vs wt-non-migratory_cells Symbol Description Median Values Fold Change Probe ID gek Flybase Entrez CMCKB genghis khan Mig: 239.3 Non-Mig: 235.7 1.01530 154234_at Discovery» Drosophila Morphology Genes Gene Name Cell Count/ Normalization Stellate11 NumCorners Stellate22 Binsum6 Non-Spreading3 CG4012 Entrez Gene: 37858 genghis khan Aliases: Genghis Kahn; Myotonic dystrophy kinase related; chingis khan 20.813 1.540 1.001 1.031 Actin: 1.123 Area: 0.918 Ratio: 1.223 CG4012
Entrez Gene: 37858 genghis khan Aliases: Genghis Kahn; Myotonic dystrophy kinase related; chingis khan 10.563 1.163 1.16 1.045 Actin: 0.995 Area: 0.975 Ratio: 1.021 Isoforms Isoform Name RefSeq Protein RefSeq mRNA Swissprot ID isoform a NP_055641 NM_014826 Q5VT25-3 isoform b NP_003598 NM_003607 Q5VT25-5
bold indicates the primary isoform Knowledgebase Home CDC42BPA (human)
Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization
Glaxo-IMCB Group, Institute of Molecular & Cell Biology, National University of Singapore, Kent Ridge, Singapore. Abstract
The Rho GTPases play distinctive roles in cytoskeletal reorganization associated with growth and differentiation. The Cdc42/Rac-binding p21-activated kinase (PAK) and Rho-binding kinase (ROK) act as morphological effectors for these GTPases. We have isolated two related novel brain kinases whose p21-binding domains resemble that of PAK whereas the kinase domains resemble that of myotonic dystrophy kinase-related ROK. These approximately 190-kDa myotonic dystrophy kinase-related Cdc42-binding kinases (MRCKs) preferentially phosphorylate nonmuscle myosin light chain at serine 19, which is known to be crucial for activating actin-myosin contractility. "...............
affirmation,,,,,,,,,,again............it is said.......... ....."These Cdc42-type effects were not promoted upon coinjection with plasmids of kinase-dead or Cdc42-binding-deficient MRCK alpha mutants. These results suggest that MRCK alpha may act as a downstream effector of Cdc42 in cytoskeletal reorganization."
It is in the smooth muscle, the light chain, the heavy chain is being removed, by the histone modification, an epigenetic, eugenetic, very selective program.
May act as a downstream effector of CDC42 in cytoskeletal reorganization. Contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation.
Catalytic activity ATP + a protein = ADP + a phosphoprotein. Ref.5
Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation.
Abundant in the heart, brain, skeletal muscle, kidney, and pancreas, with little or no expression in the lung and liver.
Biological process actin cytoskeleton reorganization
Inferred from direct assay Ref.8. Source: UniProtKB intracellular signal transduction
Inferred from electronic annotation. Source: InterPro protein phosphorylation
Inferred from direct assay Ref.5. Source: UniProtKB Cellular component cell leading edge
Inferred from sequence or structural similarity. Source: UniProtKB cell-cell junction
Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm
Inferred from electronic annotation. Source: UniProtKB-SubCell Molecular function ATP binding
Inferred from direct assay Ref.5. Source: UniProtKB identical protein binding
Inferred from physical interaction Ref.9. Source: IntAct magnesium ion binding
Inferred from direct assay Ref.5. Source: UniProtKB protein serine/threonine kinase activity
Inferred from direct assay Ref.5. Source: UniProtKB small GTPase regulator activity
Inferred from electronic annotation.
Zinc finger 1012 – 1062 51 Phorbol-ester/DAG-type
"Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion." Wilkinson S., Paterson H.F., Marshall C.J. Nat. Cell Biol. 7:255-261(2005) [PubMed: 15723050] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5), FUNCTION. Tissue: Colon.
"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS ILE-1317 AND VAL-1712. Tissue: Testis.
The end result of this transformation of humans is being done in cytoskeletal restructuring, reorganizing, remaking.....
The cytoskeleton (also CSK) is a cellular "scaffolding" or "skeleton" contained within the cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton. It has structures such as flagella, cilia and lamellipodia and plays important roles in both intracellular transport (the movement of vesicles and organelles, for example) and cellular division. The concept of a protein mosaic that dynamically coordinated cytoplasmic biochemistry was proposed by Rudolph Peters in 1929  while the term (cytosquelette, in French) was first introduced by French embryologist Paul Wintrebert in 1931.
Last Edit: May 20, 2011 22:16:50 GMT -5 by skyship
Back to Maggie Maes and Kritters reference to the c. albicans
They can change shape:
Unlike the case for mating in the haploid yeast S. cerevisiae, diploid C. albicans cells must first become homozygous at the mating-type locus (MTL), which promotes the switch from white yeast-shaped cells to mating-competent, bean-shaped opaque cells
MTL-homozygous cells switch to the opaque form at high frequency to produce mating-competent, pheromone-secreting mating partners that form shmoo mating projections (34). In the process of shmoo formation, pheromone-dependent chemotropism can occur in a biofilm which stabilizes chemotropic gradients, hence, facilitating the directed growth of mating projections toward each other (16). Chemotropism is followed by fusion and the formation of a tetraploid daughter cell (6).
..."We show here that in mating projections of both C. albicans and S. cerevisiae a Spitzenkörper-like structure is present at the growing tip and a band of septin bars is present at the base. Furthermore, in S. cerevisiae mating projections, Spa2 and Bni1 form a cap to the 3-dimensional ball of FM4-64 staining, exactly as previously observed in C. albicans hyphae, suggesting that the putative Spitzenkörper may be a distinct structure from the polarisome. Taken together this work shows that mating projections of both S. cerevisiae and C. albicans show the key characteristics of hyphal growth.
We recently showed that polarized growth in C. albicans hyphae is driven by a different mechanism compared with that in yeast and pseudohyphae (Crampin et al., 2005). Hyphal growth depends on a Spitzenkörper, whereas in yeast and pseudohyphae polarized growth depends on a polarisome. A Spitzenkörper is a vesicle-rich apical body that acts as a vesicle supply center to concentrate the delivery of secretory vesicles to the growing tip (Bartnicki-Garcia et al., 1989 blue right-pointing triangle; Virag and Harris, 2006
So the gtpase cdc 42 when not in cells will form a spitzenkorper. So, the spits is there along with the cdc42, and only forms more when the hyphae is formed. Since there are 3 forms.
Yeast form Pseudohyphae form (false hyphae) Hyphae form
GPTase = guanosine triphosphate
Pseudohyphae: "Pseudohyphae" are distinguished from true hyphae by their method of growth, relative frailty and lack of cytoplasmic connection between the cells.
* Yeast can form pseudohyphae. They are the result of a sort of incomplete budding where the cells remain attached after division.
Spitz is an organelle??
Hyphae grow at their tips. During tip growth, cell walls are extended by the external assembly and polymerization of cell wall components, and the internal production of new cell membrane.
The spitzenkörper is an intracellular organelle associated with tip growth.
It is composed of an aggregation of membrane-bound vesicles containing cell wall components. The spitzenkörper is part of the endomembrane system of fungi, holding and releasing vesicles it receives from the Golgi apparatus. These vesicles travel to the cell membrane via the cytoskeleton and release their contents outside the cell by the process of exocytosis, where it can then be transported to where it is needed.
Vesicle membranes contribute to growth of the cell membrane while their contents form new cell wall. The spitzenkörper moves along the apex of the hyphal strand and generates apical growth and branching; the apical growth rate of the hyphal strand parallels and is regulated by the movement of the spitzenkörper.
As a hypha extends, septa may be formed behind the growing tip to partition each hypha into individual cells. Hyphae can branch through the bifurcation of a growing tip, or by the emergence of a new tip from an established hypha.
Note picture on right at top, some LB patients have had this determined, Penicillium, (not penicillin), along with Cladosporium and alternaria.
The other thing I want to mention about Latex, and this is really weird, is that when I got that bulls eye rash last week after pulling the tick out of my side, I put some brown paste I bought that had all kinds of roots and herbs in it (American Indian made) over the bite area and put a (rubber) bandaid on it to keep it in.
When I post the photo, you'll see that where the adhesive ends on the bandaids were made a rash that is still on my skin as I speak. Now THAT is weird!
So, I don't know if you're referring to latex rubber, but I'll tell ya, there might be an association.
Here's the rash. Bullseye, right? Notice the two sides, esp. on left which is where the bandaid (could be reaction to the adhesive as well) caused red rash. Well, bandaids never caused a rash on me before.
Wow, it took up whole page! Anyone know why it's so large? Using the insert image feature didn't work.
Last Edit: May 24, 2011 2:26:11 GMT -5 by kritters
There has got to be a connection of some sort, but after reading everything you posted, Sky, I'm sure I'll never understand any of it or figure out the connection of any of it. I'm just a keen observer of what is in front of me and I'll have to leave the research and conclusions to you guys.
While scrounging around the latest smear campaign fall-out, I came across this article. I was shocked! Truly, something that made clear and concise sense. I imagine the article has been noted by others here, but for me, what a sweet aroma. God is being nice to me, with the plethora of deep devil doo-doo that I am wading through.
Anyway, it was like a B12 shot and I thought it may help to read it. Maybe we can get this author to take a look at the "infestation" study and comment...?
Thanks so much for bringing that great article to attention here. Whomever that author is, it's the first I've seen to make logical sense, for sure and I could have written it myself!
"...I've found serious fungal infections react to anti tinea creams. Some react to oxygen bleaches. They're anerobic, and they hate oxygen. Perhaps the Morgellons Research Foundation would like to check out reactions?..."
Everyone, this is why I questioned why some would say not to use hydrogen perixide topically or intravenously. Because they are anerobic, and they hate oxygen. Unless the Morgellons particular recombinant brand has something spliced in to love oxygen instead?
Photo-triggered release of Dexa by up-converting energy of NIR light to higher energy and indirect energy transfer from RDB grafted gum arabic bound Fe3O4 nanoparticle to the linker. (Reprinted with permission from IOP Publishing)
========================= Oparin did use "gum arabic" in forming cells.
These are the PROTOCELLS?
Oparin also used gum arabic, when making his coacervate droplets. They are supposed to prove chemical evolution and the basic laws of materialism. - What is gum arabic? From where have they taken it? - Webster’s New Collegiate Dictionary says on page 511 under gum arabic: "a water-soluble gum obtained from several acacias (esp. Acacia senegal and A. arabica)..." -
How can Oparin use gum of modern acacia trees, while trying to prove that the first living cell has evolved by itself in the dead chemical soup? Could acacia trees have grown in the primordial soup of the Early Precambrian Time, so that they could have supplied the coacervate droplets with the correct structural parts, while not even a bluegreen alga was living there yet?
..."Prof. R. W. Kaplan: "These interesting characteristics and especially their growth have caused Fox to call them ‘protocells’. This, though, should not cause us to make the mistake, to actually view them as ‘first cells’ (Greek protos = the first) and as being alive. Individualized separateness from the environment and growth alone are not enough for ‘life’. These characteristics the crystals are also showing. Also their budding, remotely reminding us of cells, for example, of yeast-cells, should not mislead us to this conclusion."
"This budding is also no dividing of primordial cells, since the budding-material is not produced anew within the cell, but comes for the surrounding proteinoid-solution. ... Similar ordering-processes, as during the assembling of several macro-molecules, are also known and understood already for a long time in the crystals, that also do arise ‘by themselves’, when the atoms come together, forming a highly ordered lattice." (1978:120, 121, 125).
Bruno Vollmert is Professor for Chemistry and Director of the Polymer Institute of the University of Karlsruhe. He says about the "pre-stages" of living cells, which Oparin, Haldane, and Fox claim to have found: "One can only wonder, with what a naivety, lacking all expert knowledge, OPARIN, HALDANE and FOX have thought out their eobionts, protobionts, and microballs as pre-stages of cells and sold them to the uncritical reader as a science - as if these quite common colloid systems had anything to do with living cells." (1983:23).'...........
* Coacervates were famously proposed by Alexander Oparin as crucial in first theory of abiogenesis (origin of Coacervates measure 1 to 100 micrometers across, possess osmotic properties and form spontaneously from certain dilute organic solutions. — “Coacervate - Wikipedia, the free encyclopedia”, en.wikipedia.org * Coacervates were the first true biological cells. They were made of a nucleus, cytoplasm and a membrane. Some of the first organic molecules formed bubble-like structures called coacervates. Coacervates were made of organic molecules surrounded by a film of water molecules. — “Life evolution, Where did we come from?, All about us (The”, skwirk.com.au * Coacervates are droplets of organic molecules that include amino Both coacervates and microspheres spontaneously form into spheres under certain conditions. — “Origin of Prokaryotes and Eukaryotes: Origin of Prokaryotes”, factmonster.com
Protocells, such as the Traube Cell, are self-assembling chemical systems with the properties of simple life forms. Dr. Rachel Armstrong developed, with a team of scientists, different types of protocells designed for various applications in urban development, namely ‘living architecture’. Armstrong aims to eventually implement an architecture that makes an autonomous contribution towards healing the environment. www.rachelarmstrong.me
A little talk of this protocell.......... and is it being used now?
Fox argued that RNA or DNA need not date back to the origin of life, and he showed that proteinoid microspheres exhibit growth, metabolism, reproduction (by budding), and responsiveness to stimuli – all properties of life – though without a genetic system. Although hesitant to claim that these were alive, Fox stated that they were undeniably “protoalive”. This is not an evasive answer. As Tim M. Berra says in Evolution and the Myth of Creationism (1990):
For centuries, science knew nothing intermediate between non-living and living things, but today the distinction is not at all clear. Since life evolved from non-living matter, at some point we must arbitrarily draw a line and say that everything beyond that point is alive. Viruses, for example, appear to be alive when they infect a host, but seem to be non-living when outside a host.
As a result of his monumental discovery of thermal proteins and their self-organization into protocells and that these protocells exhibit virtually all of the properties associated with life, Sidney Fox was invited to lecture widely throughout the world. Even Pope John Paul II and his advisers, on at least three separate occasions, invited Fox to the Vatican to explain his work on the synthesis of cellular life in a test tube.
Magnetic nanoparticle effects on the red blood cells
D E Creangă1, M Culea2, C Nădejde1, S Oancea3, L Curecheriu1 and M Racuciu4 Show affiliations
1 "Al. I. Cuza" University, Faculty of Physics, 11A Blvd. Carol I, Iasi, Romania 2 "Babes Bolyai" University, Cluj-Napoca, Romania 3 University of Veterinary Medicine "I. Ionescu de la Brad", Iasi, Romania 4 "Lucian Blaga" University, Sibiu, Romania
Tag this article Full text PDF (447 KB)
In vitro tests on magnetite colloidal nanoparticles effects upon animal red blood cells were carried out. Magnetite cores were stabilized with citric acid in the form of biocompatible magnetic fluid administrated in different dilutions in the whole blood samples. The hemolysis extent was found increased up to 2.75 in horse blood and respectively up to 2.81 in the dog blood. \ The electronic transitions assigned to the heme group were found shifted with about 500 cm-1 or, respectively, affected by supplementary vibronic structures. The Raman vibrations assigned to oxyhemoglobin were much diminished in intensity probably due to the bonding of OH group from citrate shell to the heme iron ion.
87.50.C- Static and low-frequency electric and magnetic fields effects
Modelling the interaction of electromagnetic fields (10 MHz–10 GHz) with the human body: methods and applications FEATURED ARTICLE REVIEW ARTICLE
J W H
Abstract References Cited By TOPICAL REVIEW
Numerical modelling of the interaction between electromagnetic fields (EMFs) and the dielectrically inhomogeneous human body provides a unique way of assessing the resulting spatial distributions of internal electric fields, currents and rate of energy deposition.
Knowledge of these parameters is of importance in understanding such interactions and is a prerequisite when assessing EMF exposure or when assessing or optimizing therapeutic or diagnostic medical applications that employ EMFs.
In this review, computational methods that provide this information through full time-dependent solutions of Maxwell's equations are summarized briefly. This is followed by an overview of safety- and medical-related applications where modelling has contributed significantly to development and understanding of the techniques involved. In particular, applications in the areas of mobile communications, magnetic resonance imaging, hyperthermal therapy and microwave radiometry are highlighted. Finally, examples of modelling the potentially new medical applications of recent technologies such as ultra-wideband microwaves are discussed.
87.50.S- Radiofrequency/microwave fields effects
02.70.Bf Finite-difference methods
87.55.N- Radiation monitoring, control, and safety
87.50.C- Static and low-frequency electric and magnetic fields effects Subjects
tash: Hi skizit, I have watched all your videos on youtube and cant thank you enough for all you have educated me on. I cry for you alot and a bit for me. I was wanting to send you photos of what is raining down everyday here in Australia in hope you can tell me
Dec 11, 2019 23:28:22 GMT -5
tash: not sure where to send them as hush mail and rocket mail bounced back
Dec 11, 2019 23:30:03 GMT -5