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)

p56lck, a cellular tyrosine protein kinase (EC 2.7.1.112) of the src family, is expressed in essentially all T cells and in some B cells. Expression in nonlymphoid cells is observed only rarely. We have found that mutation of a carboxyl-terminal phosphorylation site, tyrosine-505, reveals an oncogenic activity of this protein. Infection of fibroblasts with a retrovirus encoding wild-type p56lck is without consequence. In contrast, infection with a virus encoding the mutant protein leads to greatly increased phosphorylation of cellular proteins on tyrosine, morphological transformation, and anchorage-independent growth. This suggests that the tyrosine protein kinase activity and the oncogenic potential of p56lck are normally suppressed in vivo by phosphorylation of tyrosine-505. Since similar results were obtained previously with an analogous mutant of c-src, our results suggest that the protein kinase activity of all members of the src family of cytoplasmic tyrosine protein kinases will prove to be regulated by tyrosine phosphorylation at a conserved residue near the carboxyl terminus. Because p56lck is normally expressed only in lymphoid cells, it was possible that p56lck would be without effect in other tissues. The transformation of fibroblasts by mutant p56lck shows that this lymphoid protein can interact productively with nonlymphoid polypeptide substrates.
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PMID:Mutation of a site of tyrosine phosphorylation in the lymphocyte-specific tyrosine protein kinase, p56lck, reveals its oncogenic potential in fibroblasts. 338 Jul 89

Fertilization of the sea urchin egg is known to involve an increase in overall protein tyrosine kinase activity which precede the first cell division. In order to determine the types of tyrosine kinases that are involved in fertilization, we have used immunological and other criteria to identify a c-src related protein kinase in eggs of the sea urchin L. variegatus. Using an immune complex assay, we have measured the level of this c-src related protein kinase during fertilization and early embryonic development. Fertilization results in a decrease in the c-src kinase detectable by this technique suggesting that c-src does not contribute to the fertilization induced increase in protein tyrosine kinase activity.
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PMID:Quantitation of a src-like tyrosine protein kinase during fertilization of the sea urchin egg. 352 59

We isolated molecular clones of chicken DNA that carry portions of the cellular proto-oncogene c-fps and then determined the nucleotide sequence of all regions of the gene that are related to the retroviral oncogene v-fps. The homology of v-fps within c-fps resides on at least 19 interspersed segments, 17 of which represent complete exons and two of which may represent only portions of exons. Fusion of these segments reconstructs a facsimile of v-fps. The arrangement of introns and exons within c-fps differs from that of the related proto-oncogene c-src in the domains of the two genes that encode tyrosine-specific protein kinase activity. It therefore appears likely that the introns arose subsequent to the gene duplication that engendered c-src and c-fps. The data also reveal potential junctions between viral and cellular domains in the genomes of two independently isolated avian sarcoma viruses (the PRCII and Fujinami strains). The lefthand junctions can be well defined: they occur at the same position in c-fps but at different positions in the viral gene gag. The righthand junctions cannot be defined as precisely because they include a sequence of 10 to 15 nucleotides whose origin is not known. In the genome of PRCII virus, the composition of this sequence suggests that it arose from the polyadenylated 3' terminus of the c-fps messenger RNA. If this deduction proves to be correct, the data will provide direct evidence that the righthand recombination during transduction by retroviruses occurs between RNA intermediates. Irrespective of these ambiguities, both junctions are located within exons of c-fps, and both may have been formed by non-homologous recombination (although the evidence for the latter statement is not decisive). A sequence of 1020 nucleotides has been deleted from the transduced version of c-fps in the genome of PRCII virus, apparently by homologous recombination between sequences repeated within c-fps. Fujinami virus may contain the entire coding domain of c-fps, but mutations have created 26 amino acid substitutions in the viral version of the gene. By contrast, the partially deleted version of c-fps in PRCII virus contains no mutations that would alter the amino acid sequence.
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PMID:Nucleotide sequence and topography of chicken c-fps. Genesis of a retroviral oncogene encoding a tyrosine-specific protein kinase. 387 69

Two replication-defective avian sarcoma viruses, S1 and S2, which were independently isolated from tumors of chickens inoculated with avian lymphatic leukosis virus (LLV) were characterized. The genomes of S1 and S2 contain src-related sequences and are, respectively, about 3.9 and 4.5 kilobases long. pp60src-related proteins with molecular weights of 62,000 (p62) were detected in cells infected with these viruses, and protein kinase activity was found to be associated with these proteins. No other viral proteins, such as gag, pol, and env gene products, were detected. These results suggested that the c-src sequence in normal chicken cells was incorporated into LLV genomes by recombination at the expense of most of the viral genes to generate highly defective new sarcoma viruses.
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PMID:Characterization of two strains of avian sarcoma virus isolated from avian lymphatic leukosis virus-induced sarcomas. 609 28

The avian sarcoma virus-transforming gene product (pp60src) appears potentially able to mediate cell transformation via phosphorylation since it is tightly associated with a protein kinase activity. We have searched for and have been able to identify a normal cellular protein that appears to be a substrate of pp60src. The phosphorylation of this protein (34K) in transformation-specific in ASV-transformed cells of both avian and mammalian origin. Moreover, the 34K polypeptide serves as a substrate for the pp60src phosphotransferase activity in vitro and is phosphorylated at a site identical to the major site of phosphorylation in vivo. These data suggest that upon transformation the 34,000-dalton protein is phosphorylated directly as a result of pp60src activity.
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PMID:Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product. 625 69

Neoplastic transformation of pigment cells in the teleostean fish Xiphophorus is mediated by a cellular oncogene (Tu). Normally. Tu is suppressed by multiple regulating genes (R). Depending on impairment and loss of R genes, Tu is permitted to express itself phenotypically. In the pigment cell system, different degrees of Tu expression lead to small spots of transformed cells or to benign or malignant melanoma. All neoplastic and nonneoplastic cells of all Xiphophorus genotypes tested thus far appear to contain the cellular homolog (c-src) of the avian sarcoma virus oncogene (v-src). The evidence for this stems from the detectability of a Mr 60,000 phosphoprotein with associated kinase activity (pp60c-src) that reacts with antiserum against viral pp60src. We followed the inheritance of Tu (identified by spots and melanomas) compared to the expression of c-src identified by the pp60c-src-associated protein kinase). By quantitative determination of kinase activity in immunoprecipitated pp60c-src from fish showing different degrees of Tu expression, we have investigated whether there exists a correlation between the expression of c-src and Tu. In genotypes with the same genetic background, cells from Tu-containing fish express more pp60c-src than do cells from fish lacking Tu. In genotypes carrying a Tu gene and which show differences in the amount of gene expression due to a different extent of repression by regulating genes, analysis of kinase activity revealed that an increase of Tu expression is correlated with an elevated level of pp60c-src-associated kinase activity. Our findings may indicate that c-src activity in Xiphophorus is modulated by the Tu gene product or that Tu and c-src are regulated coordinately.
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PMID:Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus. 628 5

Several transformation defective (td) mutants of the Prague strain of Rous sarcoma virus, which had been previously shown to have deletions of varying sizes and positions within the src gene, were tested for their ability to induce disease in chickens. Several of the mutants induced sarcomas after long latency, in particular two mutants which had deletions spanning the presumed active site (i.e., the phosphotyrosine residue) of the RSV transforming protein, pp60src. Viruses recovered from these tumors, as well as the tumors themselves, were analyzed to study the mechanism of tumor induction. In some examples proviral DNA structurally similar to wild-type virus was found in tumors and virus recovered from these tumors was shown to transform chick cells in vitro. Transformation specific proteins of 55,000 Da immunoprecipitable with antisera against pp60src were encoded by the recovered viruses. These proteins displayed a protein kinase activity, appeared to have small deletions in the amino termini, and by phosphotryptic peptide mapping appeared to contain novel phosphotyrosine tryptic peptides, when compared to wild-type virus, which were presumably derived from endogenous c-src.
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PMID:Analysis of the pathogenicity of transformation defective partial deletion mutants of avian sarcoma virus: characterization of recovered viruses which encode novel src specific proteins. 630 17

Recently we described the isolation of c-mos (rat). The gene belongs to the family of oncogenes. Some facts render c-mos unique among the oncogenes : a) it does not contain intervening sequences and b) its expression was never detected in a large number of normal mouse tissues examined. We undertook the sequence analysis of c-mos (rat) in order to compare it to the nucleotide sequences published for c-mos (mouse), c-mos (human), c-src and bovine protein kinase. c-mos (rat) contains an open reading frame of 1017 nucleotides, coding for a polypeptide of 339 amino acids. c-mos (rat)-makes use of the same ATG that defines the N-terminus of the c-mos (human) protein. By comparing all c-mos sequences available we found sequences with high mutational rates to be confined to certain domains. This comparison, together with data on the biological activities of the cloned DNA, allowed us to tentatively define regions involved in (a) function(s) of c-mos other than transformation.
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PMID:Complete c-mos (rat) nucleotide sequence: presence of conserved domains in c-mos proteins. 632 35

Monospecific antisera prepared to denatured N and NS proteins of the Indiana serotype of VSV were used to investigate the protein associations in extracts of virus-infected cells. Complexes precipitated from the cytoplasm of infected cells with either anti-N or anti-NS serum both contained N and NS proteins but could be differentiated by the absence of any trace of M protein in the complexes precipitated with anti-NS serum. Immunoprecipitation with anti-NS serum of NS protein from the soluble cytoplasmic protein pool always resulted in coprecipitation of N protein suggesting a possible functional association of these proteins in the soluble fraction. The association of protein kinase activity with complexes containing NS protein was demonstrated by the phosphorylation of NS serine residues when immunoprecipitates containing NS protein were incubated with [32P]ATP in vitro. In protein aggregates precipitated with antibody after high salt dissociation of viral proteins it was also possible to demonstrate the presence of a c-src-like protein kinase activity as previously shown by G.M. Clinton, N.G. Guerina, H. Guo, and H.S. Huang (J. Biol. Chem. 257, 3313-3319 (1982) ).
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PMID:Protein kinase activity associated with immunoprecipitates of the vesicular stomatitis virus phosphoprotein NS. 632 12

Rous sarcoma virus (RSV) is an acutely oncogenic avian retrovirus which induces sarcomas in animals and transforms fibroblasts in cell culture. Genetic analysis indicates that the viral src gene (v-src) mediates neoplastic transformation. The product of v-src is a 60,000 molecular weight (MW) phosphoprotein (pp60v-src) possessing the enzymatic activity of a tyrosine-specific protein kinase. The viral src gene is derived from a cellular gene (c-src) which also encodes a 60,000 MW phosphoprotein (pp60c-src) with tyrosine-specific protein kinase activity. Both birds and mammals are known to possess c-src. Shilo and Weinberg have reported that the genome of the fruit fly, Drosophila melanogaster, contains nucleotide sequences that are homologous to v-src. We report here the molecular cloning and chromosomal mapping of three loci from the Drosophila genome that contain such sequences. We also show that Drosophila contain both phosphotyrosine and a tyrosine-specific protein kinase activity immunoprecipitated by antisera directed against pp60v-src. It should now be possible to identify the precise locus that encodes a src-specific protein kinase in Drosophila, and to explore the role of c-src in the growth and development of D. melanogaster.
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PMID:Three loci related to the src oncogene and tyrosine-specific protein kinase activity in Drosophila. 640 80


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