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)

Hardy-Zuckerman 2 feline sarcoma virus (HZ2-FeSV), isolated from a multicentric feline fibrosarcoma is a replication-defective acute transforming feline retrovirus which originated by transduction of feline c-abl sequences with feline leukemia virus (FeLV) and is known to encode a 110-kilodalton gag-abl fusion protein with tyrosine-specific protein kinase activity (P. Besmer, W. D. Hardy, E. E. Zuckerman, P. J. Bergold, L. Lederman, and H. W. Snyder, Nature (London) 303:825-828, 1983). The nucleotide sequence of the abl segment in the HZ2-FeSV genome was determined and compared with the murine and human v-abl and c-abl sequences. The predicted transforming protein consists of 344 amino acids (aa) of FeLV gag origin, 439 aa of abl origin, and at least 200 aa of FeLV pol origin (p110gag-abl-pol). The 1,317-base-pair HZ2-FeSV v-abl segment (fv-abl) corresponds to 5' abl sequences which include the region known to specify the protein kinase domain. The 5' 189 base pairs of fv-abl correspond to 5' c-abl sequences not contained in Abelson murine leukemia virus (MuLV) v-abl. The mouse c-abl exon which contains these segments was identified, and its nucleotide sequence was determined. Comparison of the predicted amino acid sequence of fv-abl with those of Abelson MuLV v-abl and c-abl revealed five aa differences. The 5' junction between FeLV and abl was found to involve a preferred region in FeLV gag p30 (P. Besmer, J. E. Murphy, P. C. George, F. H. Qiu, P. J. Bergold, L. Lederman, H. W. Snyder, D. Brodeur, E. E. Zuckerman, and W. D. Hardy, Nature (London) 320:415-421, 1986). A six-base homology exists at the recombination site between the parental FeLV and the c-abl sequences. The 3' junction between fv-abl and FeLV pol predicts an in-frame fusion of fv-abl and FeLV pol. A transformed cell line containing a truncated gag-abl-pol protein, p85, that lacks most of the FeLV pol sequences was obtained by transfection of NIH 3T3 mouse cells. This result implies that the pol sequences of the p110gag-abl-pol protein are dispensable for fibroblast transformation. To assess whether the fv-abl segment specifies the unique biological properties of HZ2-FeSV, we constructed a Moloney MuLV-based version of HZ2-FeSV, Mo-MuLV(fv-abl), in which the fv-abl sequences were contained in a genetic context similar to that in HZ2-FeSV.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nucleic acid sequence and oncogenic properties of the HZ2 feline sarcoma virus v-abl insert. 302 15

We have isolated cDNA molecules representing the complete coding sequence of a new human gene which is a member of the src family of oncogenes. Nucleotide sequence analysis revealed that this gene, termed slk, encoded a 537-residue protein which was 86% identical to the chicken proto-oncogene product, p60c-src, over a stretch of 191 amino acids at its carboxy terminus. In contrast, only 6% amino acid homology was observed within the amino-terminal 82 amino acid residues of these two proteins. It was possible to activate slk as a transforming gene by substituting approximately two-thirds of the slk coding sequence for an analogous region of the v-fgr onc gene present in Gardner-Rasheed feline sarcoma virus. The resulting hybrid protein molecule expressed in transformed cells demonstrated protein kinase activity with specificity for tyrosine residues.
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PMID:Isolation and oncogenic potential of a novel human src-like gene. 309 69

We have generated a cDNA copy of human c-fps/fes from a 13 kb genomic DNA by means of a retroviral shuttle vector, and have begun characterization of its biological and biochemical properties. The cDNA was able to direct the in vitro synthesis of a protein that was indistinguishable from myeloid cell c-fps/fes NCP92 by immunoprecipitation with specific antisera, electrophoretic mobility, tryptic fingerprint analysis, and its associated protein kinase activity. When the coding sequence of the gag-v-fps/fes P108 fusion protein in Gardner Arnstein Feline sarcoma virus was substituted with the recovered cDNA, the recombinant plasmid directed the expression of NCP92 in NIH 3T3 cells but no morphological transformation was observed. By contrast, when viral gag sequences were linked to the N-terminus of NCP92, the chimeric gene induced foci of transformed cells. These transformants were capable of anchorage independent growth, were tumorigenic in nude mice, and expressed a gag fusion protein kinase of high specific activity. The biological properties of this recombinant are discussed. We conclude that normal human c-fps/fes can be activated by N-terminal linkage to gag.
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PMID:Human cellular fps/fes cDNA rescued via retroviral shuttle vector encodes myeloid cell NCP92 and has transforming potential. 332 18

The Gardner and Snyder-Theilen isolates of feline sarcoma virus (FeSV) have previously been shown to encode high-molecular-weight polyproteins with a transforming function and an associated tyrosine-specific protein kinase activity. Cells transformed by these viruses exhibited morphological alterations, elevated levels of phosphotyrosine, and a reduced capacity for binding epidermal growth factor. In addition, polyproteins encoded by both of these FeSV isolates bound to, and phosphorylated tyrosine acceptor sites within, a 150,000-molecular-weight cellular substrate (P150). McDonough FeSV-transformed cells resembled Gardner and Snyder-Theilen FeSV transformants with respect to morphological changes and a reduced capacity for epidermal growth factor binding. in contrast to the other two FeSV isolates, however, McDonough FeSV encoded as its major translational product a high-molecular-weight polyprotein with probable transforming function but without protein kinase activity detectable under similar assay conditions. Moreover, total cellular levels of phosphotyrosine remained unaltered in McDonough FeSV-transformed cells, and the major McDonough FeSV polyprotein translational product lacked binding affinity for P150. These findings argue for differences in the mechanisms of transformation by these independently derived FeSV isolates.
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PMID:Differences in mechanisms of transformation by independent feline sarcoma virus isolates. 616 38

Cells nonproductively transformed by a variant of the Snyder-Theilen strain of feline sarcoma virus (FeSV) expressed an 85,000-dalton polyprotein (P85) with associated tyrosine-specific protein kinase activity. We identified within this polyprotein a single tyrosine acceptor site for its enzyme activity. This acceptor site, as well as two serine phosphorylation sites localized with the p12 structural component of Snyder-Theilen FeSv P85, was phosphorylated in cells nonproductively transformed by Snyder-Theilen FeSv. In contrast, infection by Snyder-Theilen FeSV transformation-defective mutants resulted in phosphorylation only of the two serine acceptor sites, indicating phosphorylation of the tyrosine acceptor site to be transformation specific. In addition, we describe in vitro labeling conditions, using unfractionated cell extracts, which resulted in preferential phosphorylation of the single Snyder-Theilen FeSV tyrosine-specific acceptor site.
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PMID:Snyder-Theilen feline sarcoma virus P85 contains a single phosphotyrosine acceptor site recognized by its associated protein kinase. 616 40

Four phenotypically normal mink cell clones, each containing a transformation-defective provirus of the Snyder-Theilen strain of feline sarcoma virus (ST-FeSV), synthesized an 85,000-dalton viral polyprotein (P85) indistinguishable in size and antigenic complexity from that encoded by wild-type transforming ST-FeSV. An additional transformation-defective, ST-FeSV-containing flat cell clone produced a polyprotein of 88,000 daltons (P88). The viral polyproteins immunoprecipitated from cytoplasmic extracts of these cells lacked the tyrosine-specific protein kinase activity associated with the wild-type ST-FeSV gene product. In addition, the products encoded by representative transformation-defective ST-FeSV genomes were poorly phosphorylated in vivo and lacked detectable phosphotyrosine residues. Whereas proteins of ST-FeSV transformants contained elevated levels of phosphotyrosine, those of mink cells containing transformation-defective ST-FeSV exhibited phosphotyrosine levels no higher than those found in uninfected cells. These findings provide genetic evidence that the tyrosine-specific protein kinase activity associated with ST-FeSV P85 is required for virus-induced transformation.
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PMID:Transformation-defective mutants of Snyder-Theilen feline sarcoma virus lack tyrosine-specific protein kinase activity. 616 71

Hybridomas secreting monoclonal antibodies directed against polyprotein gene products of the Gardner, Snyder-Theilen, and McDonough strain of feline sarcoma virus have been isolated. Antibody produced by one hybridoma recognizes immunological determinants localized within a feline leukemia virus gag gene structural component (p15) common to polyproteins encoded by each feline sarcoma virus isolate while antibody produced by a second is specific for p30 determinants unique to P170gag-fms. Additional hybridomas secrete antibody directed against v-fes specific determinants common to the Gardner and Snyder-Theilen feline sarcoma virus-encoded polyproteins and to v-fms determinants unique to P170gas-fms polyprotein. GA P110gas-fes and ST P85gas-fes immunoprecipitated by antibody directed against p15 exhibit readily detectable levels of protein kinase activity but lack such activity when precipitated by antibody specific for their acquired sequence (v-fes) components. P170gas-fms immunoprecipitated by monoclonal antibody to either p15 or p30 lacks detectable levels of autophosphorylation but represents a substrate for the GA P110gag-fes and ST P85gag-fes enzymatic activities. These findings argue that the v-fes-associated protein kinase represents an intrinsic property of the v-fes gene product and recognizes tyrosine acceptor sites within polyprotein gene products of all three strains of feline sarcoma virus.
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PMID:Monoclonal antibodies specific to transforming polyproteins encoded by independent isolates of feline sarcoma virus. 618 42

Polyproteins (gag-fes) encoded by the Synder-Theilen (ST) and the Gardner-Arnstein (GA) strains of feline sarcoma virus (FeSV) were previously shown to be associated with mink or rat cells that were nonproductively transformed in vitro. In the present study we demonstrated that the same gag-fes proteins were found in cat cells transformed in vitro. Of greater importance, these transformation-related proteins were also in cells taken from fresh biopsies of FeSV-induced tumors. Cells from fibrosarcomas induced with ST-FeSV had gag-fes proteins that were characteristic of this strain. Fibrosarcomas and melanomas were induced with GA-FeSV and both types of tumors contained the protein that is characteristic of cells transformed in vitro with this virus. Expression of these proteins in cultured tumor cells appeared to be independent of the passage level. Based on two-dimensional tryptic peptide analysis, the gag-fes proteins of cat tumor cells appeared to be indistinguishable from those found in cells transformed in vitro. The polyproteins of the cat tumor cells have a closely associated protein kinase activity, as demonstrated in the in vitro assay, and phosphorylated tyrosine residues. Gag-fes proteins of either the ST or GA class were not present in cell cultures initiated from five spontaneous cat tumors.
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PMID:Feline sarcoma virus-specific transformation-related proteins and protein kinase activity in tumor cells. 618 75

Protein phosphorylation by a tyrosine-specific kinase is now recognized as a common event in retrovirus-transformed cells. We report in this communication that the feline sarcoma virus (FeSV) encoded transformation-specific proteins (gag-fes fusion proteins) and their associated protein kinases are also found in the FeSV in vivo induced tumor preparations, either in the form of fresh tumor homogenate or in the form of cultured cells. With the combined use of subcellular fractionation and detergent extraction we found that the protein kinase activity was present in both the membrane fraction (P100) and the cytosol (S100). The gag-fes proteins of two different strains of FeSV were found to associate with the cell framework to different degrees, suggesting that the specific conformational presentation of these proteins may be dictated by the unique portion of each polyprotein. The same gag-fes transformation related proteins could be immunoprecipitated with antiserum to phosphotyrosine.
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PMID:Detection and localization of a phosphotyrosine-containing onc gene product in feline tumor cells. 619 Jul 15

A new feline sarcoma virus designated Theilen-Pedersen (TP1-FeSV) has been isolated from a spontaneous, slowly growing fibrosarcoma of a domestic short-haired 4-year-old castrated cat. The virus codes for a gag-onc fusion protein of 83,000 molecular weight phosphorylated in vivo at serine, threonine, and tyrosine residues. Cells transformed in vitro with TP1-FeSV exhibit five- to 10-fold elevated levels of phosphotyrosine over FeLV-infected cells. The gag-onc polyprotein has associated with it a tyrosyl protein kinase activity which in vitro results in autophosphorylation of the molecule at tyrosine residues. The fusion protein cannot be labeled metabolically with [3H]glucosamine and tunicamycin has no effect on the electrophoretic mobility of the in vivo [32P]orthophosphate-labeled fusion protein. The fusion protein, in common with the gag precursor Pr65gag, can be metabolically labeled with palmitic acid.
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PMID:Biological and biochemical characterization of a new isolate of feline sarcoma virus: Theilen-Pedersen (TP1-FeSV). 620 83


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