Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The deduced amino acid sequences of the open reading frames (ORFs) mapping in the short unique segment (US) of Marek's disease virus (MDV) reported in the accompanying paper have been analysed using computer programs to determine their relationships to herpesvirus proteins. Analysis of the catalytic domains of protein kinases showed that the MDV kinase (MDV PK) was closely related to the alphaherpesvirus protein kinase mapping in US. The results also showed that the MDV PK was more closely related to the cellular kinases that control cell division than to the proto-oncogenes c-src and c-mos and it was predicted that the MDV PK would phosphorylate serine/threonine. The MDV homologue of herpes simplex virus (HSV) glycoprotein D (gD) contained several residues that were conserved in mammalian herpesviruses. In particular, six cysteines were perfectly aligned in all the gDs and there were numerous conservative substitutions. Although only approximately 65% of the MDV homologue of glycoprotein I (gI) of HSV has been sequenced, it was clear that a significant number of amino acid residues including four cysteines were conserved in the gI homologues of MDV and mammalian herpesviruses. Further analysis suggested that MDV gD was more closely related to the gDs of pseudorabies virus (PRV) and equine herpesvirus 1 than to the gD of HSV-1 and HSV-2. It was noted that HSV-2 glycoprotein G (gG), PRV gX and MDV gD were related and that MDV ORF4 was related to MDV gD and probably to HSV-1 gG. The results have shown a clear relationship between the genes of MDV and their counterparts in mammalian alphaherpesviruses and are consistent with the idea that MDV glycoprotein genes in US might have arisen by a process of gene duplication and independent evolution.
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PMID:Properties and evolutionary relationships of the Marek's disease virus homologues of protein kinase, glycoprotein D and glycoprotein I of herpes simplex virus. 184 76

A tyrosine-protein kinase was purified more than 270-fold from the rat liver plasma membrane fraction by successive column chromatographies on Sephacryl S-300, wheat germ agglutinin-agarose, casein-Sepharose, and hydroxylapatite, followed by isoelectrofocusing electrophoresis. The enzyme with pI of 6.2 was a 60-kDa single polypeptide which represented 42% of total protein. The enzyme reacted quantitatively with a monoclonal antibody to the amino-terminal sequence (Cys-3 to Ser-66) specific to the human c-yes protein, but not with antibodies to the specific amino-terminal sequences of the c-src, fyn, and lck proteins. The purified enzyme contained almost no phosphotyrosine residue but was autophosphorylated with Mg.ATP exclusively at tyrosine residues with concomitant increase in the kinase activity. The rates of autophosphorylation of the enzyme and phosphorylation of tyrosine-glutamate (1:4) copolymers, catalyzed by the enzyme were proportional to the square of enzyme concentration, suggesting that p60c-yes undergoes autophosphorylation through intermolecular catalysis, resulting in stimulation of the enzyme activity. Although the enzyme reaction showed an essential requirement for Mg2+ or Mn2+ with optimal concentrations of 20 and 3 mM, respectively, autophosphorylation significantly activated the enzyme only in the presence of Mg2+. Autophosphorylation of the enzyme reduced the Km for tyrosine-glutamate copolymers and tubulin, but not for ATP, and increased the Vmax of copolymer and tubulin phosphorylation.
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PMID:Purification and characterization of a rat liver membrane tyrosine-protein kinase, the possible protooncogene c-yes product, p60c-yes. 200 30

The product of the c-src proto-oncogene (pp60c-src) is a tyrosine-specific protein kinase that is expressed in two phases of neural development. In post-mitotic neuronal cells undergoing terminal differentiation, pp60c-src is present at high levels in the membrane of nerve growth cones and proximal axon shafts. Membrane-associated forms of alpha- and beta-tubulin are the major phosphotyrosine-modified proteins in growth cone membranes in vivo. pp60c-src phosphorylates purified, unassembled tubulin subunits in vitro, inhibiting their ability to polymerize into microtubules. It is conceivable that tubulin phosphorylation by pp60c-src in the growth cone may regulate neurite extension by altering adhesion of cells to the substratum.
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PMID:Tyrosine phosphorylation of membrane-associated tubulin in nerve growth cones enriched in pp60c-src. 211 26

A recombinant baculovirus was constructed for the production of the serine-specific protein kinase, pp90rsk (where rsk is ribosomal S6 kinase), in insect cells. The Xenopus pp90rsk expressed in the infected cells had nearly undetectable enzyme activity in contrast to the same enzyme coproduced with the v-src oncogene product pp60v-src. The transforming gene product pp60v-src very effectively activated pp90rsk, whereas the products of c-src and the myristoylation-minus nontransforming virus NY315 were markedly less effective. Only a fraction of the total pp90rsk population was activated, and it could be partially separated from unactivated protein by ion-exchange chromatography. When compared to the unactivated form, the activated enzyme displayed about a 4000-fold increase in the capacity to phosphorylate the ribosomal protein S6. The enhanced enzymatic activity appeared to be due to phosphorylation of pp90rsk.
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PMID:Coinfection of insect cells with recombinant baculovirus expressing pp60v-src results in the activation of a serine-specific protein kinase pp90rsk. 213 82

We have isolated four activated transforming human c-src mutants derived spontaneously from viruses carrying the normal human c-src (SRC) genes in the form of Rous sarcoma virus. These mutants induced transformed cell morphology distinguishable from each other in vitro as well as tumors in chicks, whereas normal SRC-carrying viruses did not. Analyses of the transforming SRC proteins together with the normal SRC protein showed that levels of the carboxy-terminal Tyr-phosphorylation were negatively correlated with both transforming ability and protein kinase (PKase) activity as determined by in vitro autophosphorylation. It was observed that two cell lysis methods, that is, NP-40 and RIPA, yielded two different phosphorylated forms of transforming SRC proteins: one possessed low levels of phosphorylation at the autophosphorylation site and the other possessed high levels of phosphorylation at this site. Using the two types of transforming SRC preparations, we have studied in vitro SRC-PKase reactions in relation to in vivo and in vitro autophosphorylation and in vitro phosphorylation of an exogenous substrate. A possible functional relationship between autophosphorylation and SRC-PKase expression is discussed.
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PMID:Characterization of avian retroviruses carrying activated transforming human c-src genes and of steps involved in expression of activated src-PKases in vitro. 216 36

Three different types of experiments are presented in this paper, the results of which converge to indicate that the viral src protein associates with and modulates the activity and/or the specificity of a serine/threonine protein kinase. Firstly, a 60-kDa protein from extracts of FR3T3 rat fibroblasts transformed by wild-type Rous sarcoma virus (SRD-FR3T3) is shown to be immunoprecipitated with a monoclonal antibody (mAb) raised against bacterially produced pp60v-src, the mAb327 [Lipsich, L. A., Lewis, A. J. & Brugge, J. S. (1983) J. Virol. 48, 352-360] and to be phosphorylated in vitro at serine/threonine/tyrosine residues, in the ratio 25:53:22. Under the same experimental conditions, the pp60c-src protein immunoprecipitated with mAb327 from extracts of NIH c-src overexpresser cells is phosphorylated exclusively on tyrosine residues. Secondly, the results of immunoprecipitation experiments using a tumor-bearing rabbit (TBR) serum and reported in an earlier work [David-Pfeuty, T. & Hovanessian, A. (1984) Eur. J. Biochem. 140, 325-342], together with those reported here, suggest that the TBR-immunoprecipitated pp60v-src coprecipitates with a cellular protein related to the 60-kDa subunit of the Ca2+/calmodulin protein kinase II from brain. Finally, partially purified preparations of pp60v-src, but not of pp60c-src, are shown to contain a Ca2+/calmodulin-dependent protein kinase activity that phosphorylates a 52-kDa protein substrate.
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PMID:Serine/threonine-specific protein kinase activity associated with viral pp60src protein. 216 17

A frameshift mutation, arising from the deletion of any one of nine consecutive cytidines in the region of Py DNA encoding both the midregion of large T-Ag and the C-terminal region of middle T-Ag, yields unstable flat cell revertants that synthesize two novel viral proteins in which shuffling of the different domains of the Py T-Ags has occurred. The first protein (37 kd) is a hybrid containing the N-terminus of large T-Ag and the hydrophobic C-terminus of middle T-Ag. The latter domain is responsible for membrane association, even in the 37 kd hybrid protein. The second protein (43 kd), which contains the N-terminal 75% of middle T-Ag, has an associated protein kinase activity and forms a complex with c-src, but cannot induce a transformed phenotype.
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PMID:A frameshift at a mutational hotspot in the polyoma virus early region generates two new proteins that define T-antigen functional domains. 241 29

Expression of p60v-src of Rous sarcoma virus in cultured chicken embryo neuroretinal cells was previously shown to result in the transformation and sustained proliferation of normally quiescent cell populations. We show here that Rous sarcoma virus variants that encode p60c-src, the cellular homolog of p60v-src, lack the ability to induce morphological transformation and cell proliferation of cultured neuroretinal cells. Neuroretinal cells infected with c-src-containing viruses, however, possess no less p60 protein kinase activity assayed in the immune complex than those infected with the transformation-defective Rous sarcoma virus mutants PA101 or PA104, which do stimulate the growth of these cells.
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PMID:Lack of induction of neuroretinal cell proliferation by Rous sarcoma virus variants that carry the c-src gene. 242 77

The acutely-transforming avian virus, Rous sarcoma virus, arose as the result of the transduction of the c-src gene of the chicken by a relatively benign avian leucosis virus. In the viral genome, the src gene is expressed in the form of a 60 kDa phosphoprotein, pp60v-src, which is a protein-tyrosine kinase. Cellular transformation results from the excessive or chronic phosphorylation of cellular proteins by pp60v-src. The c-src gene has been present in the genome of eukaryotes, at least since the evolutionary emergence of Drosophila. Like its viral descendant, it encodes a 60 kDa protein-tyrosine kinase, termed pp60c-src. Both pp60v-src and pp60c-src are bound to membranes. pp60c-src is expressed at low levels in most cell types but it is found in high amounts in neural tissues and in platelets. pp60c-src might therefore participate in vesicle-mediated secretion. pp60c-src is less active as a protein-tyrosine kinase then pp60v-src and does not induce cellular transformation, even when expressed at levels comparable to those of pp60v-src. The potency of pp60v-src apparently results from the fact that the region of the c-src gene encoding the C terminus of pp60c-src was lost during the genesis of the v-src gene. This region of pp60c-src contains a site of tyrosine phosphorylation whose occupancy apparently leads to diminished enzymatic activity. The deletion of this site may abolish the normal regulation of the protein kinase activity. If so, transformation could simply be the consequence of the inability of the cell to regulate the activity of pp60v-src.
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PMID:From c-src to v-src, or the case of the missing C terminus. 243 Jul 1

We studied the expression of a molecularly cloned human c-src gene, c-src-1, localized on chromosome 20, whose coding region consists of 11 exons and spans a 19.5-kilobase (kb) distance. Using a replication-competent retroviral vector derived from molecularly cloned Rous sarcoma virus DNA (pSRA-2), we obtained two constructs: one (pSR-CS) carrying the unmodified human c-src coding sequence and another (pSR-CVS) with a chimeric gene formed between the human c-src gene and the carboxy-terminal 12-amino acid v-src-specific coding sequence. From chicken embryo fibroblasts transfected with these DNA constructs, infectious viruses designated as WO CS and WO CVS, respectively, were recovered. WO CS virus did not cause cell transformation, whereas WO CVS induced cell transformation. Analyses of the proviral DNAs indicated that all introns were spliced out such that the 19-kb inserts were converted to 1.7-kb cDNA forms. Analyses of src proteins in infected cells, using monoclonal antibody MAb327 against v-src protein, showed the following results. The CVS and CS src proteins were about 60 and 61 kilodaltons in size, respectively; the specific protein kinase activity assayed in vitro of the CVS src protein was about 20-fold higher than that of the CS src protein and comparable to that of the v-src protein; the transforming CVS src protein reacted to an antibody against a v-src-specific peptide, whereas the CS src protein did not. These results indicate that the human c-src gene has a potential transforming ability and suggest that the v-src-specific sequence played an important role in the generation of Rous sarcoma virus.
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PMID:Expression of a molecularly cloned human c-src oncogene by using a replication-competent retroviral vector. 243 94


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