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 transmembrane potential of Rous sarcoma virus (RSV)-infected Rat-1 cells, expressing the pp60v-src protein kinase, is markedly less negative (by approximately 30 mV) than that of their normal counterparts. By contrast, the membrane potential of Rat-1 cells infected with Kirsten sarcoma virus is virtually unaltered. The RSV-induced membrane depolarization is shown to be due to a severalfold increase in the cation permeability ratio (PNa/PK) of the plasma membrane. When cells infected with a temperature-sensitive mutant of RSV (ts LA29), encoding a src protein with heat-labile kinase activity, are shifted from the nonpermissive to the permissive temperature, a rapid and sustained membrane depolarization is observed. Conversely, thermal inactivation of the ts LA29 pp60v-src kinase activity rapidly restores the membrane potential to near normal levels. Addition of epidermal growth factor, platelet-derived growth factor, or insulin to uninfected cells fails to cause a detectable change in membrane potential. We conclude that, unlike growth factor receptor tyrosine kinases, pp60v-src can induce, either directly or indirectly, a major change in the membrane permeability to monovalent cations.
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PMID:Expression of pp60v-src alters the ionic permeability of the plasma membrane in rat cells. 243 84

Subcellular localization of potential substrates of a tyrosine-protein kinase, p60v-src, was analyzed by cell fractionation in combination with immunoblotting with antiphosphotyrosine antibody. In cells transformed by wild type Rous sarcoma virus, most phosphotyrosine-containing proteins were found both in plasma membranes and in a cytoplasmic matrix structure associated with plasma membranes and resistant to nonionic detergent extraction (plasma membrane matrix). A similar localization of phosphotyrosine-containing proteins was obtained in cells transformed by PRCII, Y73, or Fujinami sarcoma virus. On the other hand, in cells infected with Rous sarcoma virus mutants that encode nonmyristylated p60v-src, tyrosine phosphorylation was found mostly in proteins which were different from those identified in wild type-infected cells and were distributed to both plasma membrane and cytosolic fractions. These results suggest that most cellular substrate proteins, phosphorylation of some of which may be critical for the initiation of transformation, are present primarily in the plasma membrane-matrix structure.
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PMID:Localization of major potential substrates of p60v-src kinase in the plasma membrane matrix fraction. 249 23

Previous studies have shown that vimentin, an intermediate filament protein, is reduced in amount in cells acutely infected with Moloney mouse sarcoma virus (Mo-MuSV). In this report, we provide evidence for specific alteration of vimentin in Mo-MuSV-transformed cells and demonstrate specific phosphorylation of vimentin by the p37mos protein kinase in vitro. Specificity of the phosphorylation reaction was demonstrated by using viral mos proteins encoded by various isolates of Mo-MuSV and p37mos produced in yeast. A phosphotransfer domain mutant lacking the ability to autophosphorylate p37mos failed to phosphorylate vimentin. Similarly, vimentin was not phosphorylated by the temperature-sensitive P85gag-mos kinase derived from infected cells maintained at the restrictive temperature. In ts110 MuSV-transformed NRK cells, vimentin was phosphorylated at both the permissive and nonpermissive temperatures for transformation. However, at the permissive temperature, an altered form of vimentin (about 50 kDa) with a more basic isoelectric point and lower apparent molecular weight was detected. This 50-kDa product was highly phosphorylated as compared to the bulk of the normal 55-kDa form of vimentin. On the basis of its mobility in two-dimensional gels, the 50-kDa form of vimentin should lack the carboxy terminus. This type of alteration could conceivably modulate the function of vimentin filaments in the transformed cell.
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PMID:Vimentin phosphorylation by p37mos protein kinase in vitro and generation of a 50-kDa cleavage product in v-mos-transformed cells. 255 68

A Mr 74,000 phosphoglycoprotein (gp74) present on the surface of oncogene-transformed murine cells but not untransformed NIH 3T3 cells was previously identified with mouse monoclonal antibody 45-2D9. The original cell population used as the immunogen was found to consist of two cell populations. The purpose of this study was to characterize these cell populations; determine the distribution of gp74 on normal, transformed, and neoplastic cells; and to characterize the gp74 molecule. Southern hybridization studies of cloned cell populations demonstrated that the immunizing cell population consisted of c-Ha-ras-transfected NIH 3T3 cells and Kirsten sarcoma virus-transformed rat cells (TRF cells). TRF cells showed a high level of gp74 expression. We observed that the expression of gp74 was increased on chemically and spontaneously transformed rat cells compared to untransformed rat cells. No binding of monoclonal antibody 45-2D9 was detected to rat adult and fetal tissue. Immunoperoxidase staining, immunofluorescence flow cytometry, and immunoprecipitation analysis of dimethylbenz[a]anthracene-induced metastatic 13762NF rat mammary adenocarcinoma clonal sublines demonstrated an inverse relationship between gp74 expression and metastatic phenotype. gp74 was immunoprecipitated from two low and medium metastatic clonal sublines (MTC and MTF7), but not from highly metastatic clone MTLn3 cells. Biosynthetic labeling and immunoprecipitation studies demonstrated that gp74 was phosphorylated on serine residues and was not secreted from transformed cells. No detectable protein kinase activity in an immune complex assay was associated with this molecule. We conclude that increased gp74 expression by rat cells is associated with transformed and neoplastic cells.
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PMID:Analysis of expression of cell surface antigen Mr 74,000 phosphoglycoprotein in normal, oncogene-transformed, and neoplastic rat cell lines. 265 Aug 64

We have developed a one-step purification procedure for proteins containing the N-terminal portion of the gag protein of avian sarcoma and leukemia viruses. In this procedure, a resin with a covalently attached monoclonal antibody to the gag protein p19 is used to bind gag-containing proteins from crude extracts. After washing of the resin, the bound proteins are eluted with 2 M MgCl2. For the transforming protein kinase encoded by Fujinami sarcoma virus p130gag-fps, this procedure gave an enrichment of several thousand-fold, a yield of over 10%, a final purity of over 20%, and no significant loss of protein kinase activity. Similar purifications were obtained with three other gag-containing proteins. The immunoaffinity purification described may be of general utility as a first step in purification of the several other avian retroviral transforming proteins that are synthesized from fusions of an oncogene with the viral gag gene.
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PMID:A simple method for immunoaffinity purification of nondenatured avian sarcoma and leukemia virus gag-containing proteins. 282 89

The cellular mutant B812 isolated from a Fisher rat cell line shows temperature sensitivity of focus formation induced by various retroviruses such as recombinant murine retrovirus containing the middle T gene of polyomavirus (PyMLV), Kirsten murine sarcoma virus, Moloney murine sarcoma virus, and recombinant murine retrovirus containing the src gene of Rous sarcoma virus. B812 cells, however, show normal ability to proliferate and synthesize protein at the nonpermissive temperature, suggesting that their mutation is in a gene specifically concerned with the process of transformation by retroviruses. In this work, experiments with hybrids of mutant and wild-type cells showed that the temperature-dependent defect of this mutant was complemented by wild-type cells. To determine the step of transformation that is restricted at the nonpermissive temperature in B812, we examined the expressions of the oncogene (middle T antigen) in no. 7 (wild-type cells) and B812 cultures infected with PyMLV (the chimeric retrovirus containing the middle T gene of polyomavirus) at the permissive and nonpermissive temperatures. Middle T-associated protein kinase activity, the expression of middle T antigen, and PyMLV-specific mRNA were reduced at the nonpermissive temperature in B812 cultures infected with PyMLV. However, integration of PyMLV into the chromosomal DNA of the mutant was not affected at the nonpermissive temperature. These results suggest that B812 cells have a mutation affecting the expression of viral mRNAs from integrated proviral DNA at the nonpermissive temperature.
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PMID:Temperature-sensitive cellular mutant for expression of mRNA from murine retrovirus. 282 38

Site-selective cAMP analogs, depending on the position of their substituents on the adenine ring, selectively bind to either site 1 or site 2 of the known cAMP binding sites of protein kinase. Treatment of Harvey murine sarcoma virus-transformed NIH/3T3 cells with such site-selective analogs results in growth inhibition and phenotypic reversion, and the combination of a C-8 thio or halogen analog (site 1 selective) with an N6 analog (site 2 selective) produces a synergistic effect. We report here that the growth inhibitory effect of the analogs correlates with the nuclear translocation of the RII cAMP receptor protein, the regulatory subunit of protein kinase type II. The transformed NIH/3T3 cells contained no detectable level of RII in the nucleus, whereas nontransformed NIH/3T3 cells exhibited a high level of nuclear RII. Within 30 min after treatment of the transformed cells with the site-selective analogs, immunofluorescence against the RII protein markedly increased in the cell nucleus. The nuclear translocation of the RII cAMP receptor protein is an early event in the reverse transformation of the fibroblasts treated with site-selective cAMP analogs.
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PMID:Site-selective cAMP analogs induce nuclear translocation of the RII cAMP receptor protein in Ha-MuSV-transformed NIH/3T3 cells. 282 32

Eighteen site-selective cAMP analogs modified at either the C-8 position or the C-6 position were tested for their growth regulatory effects on the Harvey murine sarcoma virus-transformed NIH/3T3 clone 13-3B-4 cells grown in a serum-free defined medium. All 18 analogs, when tested individually, exhibited an appreciable growth inhibitory effect at micromolar concentrations. The most potent growth inhibitory analogs contained a thio moiety at the C-8 position. In general, C-6 analogs required 5-10-fold greater concentrations than C-8 analogs to produce the same degree of growth inhibition. The growth inhibition induced by these analogs was accompanied by a change in cell morphology; cells treated with the analogs exhibited the morphology characteristic of untransformed fibroblasts, while untreated cells retained a transformed phenotype. The regulatory subunit of cAMP-dependent protein kinase, the cAMP receptor protein, has two different intrachain cAMP binding sites, and cAMP analogs modified at the C-8 position (C-8 analogs) are generally selective for Site 1, while analogs modified at the C-6 position (C-6 analogs) are generally selective for Site 2. Thus, C-8 and C-6 analogs were tested in combination to enhance the growth regulatory effect. Both growth inhibition and morphological change were enhanced synergistically by a combination of the C-6 and C-8 analogs. Two C-6 analogs or two C-8 analogs added together did not cause synergism. For both growth inhibition and phenotypic change, C-8 thio analogs acted far more synergistically than C-8 amino analogs when cells were treated in combination with C-6 analogs, suggesting a response of the RII rather than the RI cAMP receptor protein. DEAE-cellulose chromatography revealed that the growth inhibition, in fact, correlates with an increase of the RII cAMP receptor protein and a decrease of the RI receptor protein. The growth inhibitory effect of the site-selective analogs was not due to the cytotoxic effect of adenosine metabolites as shown by the different behavior of 8-Cl-cAMP compared with 8-Cl-adenosine in 1) cell cycle effects and 2) release from growth inhibition. It is concluded that the observed growth inhibition and phenotypic reversion of 13-3B-4 cells is most likely mediated through the cellular effector, the RII cAMP receptor protein.
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PMID:Reverse transformation of Harvey murine sarcoma virus-transformed NIH/3T3 cells by site-selective cyclic AMP analogs. 282 44

A procedure for measuring the activity of tyrosine-specific protein kinases was developed. The method is based on the fact that the phosphoryl groups of phosphotyrosine residues of phosphorylated protein substrates are not hydrolyzed in alkaline solutions, whereas the phosphoserine and phosphothreonine residues lose their phosphoryl groups upon heating in 2 N KOH. It was demonstrated that rat sarcoma XC cells in culture and in solid tumours contain tyrosine-specific protein kinase (TPK). The TPK is localized in the membrane fraction of the cells and is solubilized by 1% Triton X-100. Mn2+-ATP is a nucleotide substrate for TPK. Among other protein substrates, TPK strongly phosphorylates histones H5 and H2a, weakly phosphorylates histones H2b, H4 and H1 but does not phosphorylate protamine, casein, vinculin or angiotensin II. The optimal concentration of Mn2+ for the reaction is 2 mM; the Km values for ATP and histone H5 are 2-3 microM and 2.5 mg/ml, respectively. Tyrosine-specific protein kinases phosphorylating histone H5 were detected in the membrane fraction isolated from different mammalian tissues, e. g., spleen, heart, liver, brain and lungs, as well as from human intestinal mucosa and mucosal adenocarcinoma. These results suggest that tyrosine-specific protein kinases phosphorylating histone H5 are present in a vast majority of mammalian tissues.
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PMID:[Properties of tyrosine-specific protein kinase from rat sarcoma cells]. 283 Sep 13

The mos oncogene present in Moloney murine sarcoma virus is one of the oldest known oncogenes, yet the identification of its biochemical function both in transformation and as a cellular proto-oncogene has been elusive. Only recently have low levels of c-mos transcripts been detected in a specific group of mouse tissues. The c-mos gene is implicated in tumorigenicity by its activation by the insertion of the intracisternal A particle genome in a mouse plasmacytoma. The murine c-mos gene is capable of oncogenic transformation when placed under the regulatory control of a long terminal repeat. The acquisition of the v-mos gene generated the transformation-competent Moloney murine sarcoma virus and several related strains. Myeloproliferative sarcoma virus is unique among the v-mos containing viruses in its ability to induce splenic foci and myeloproliferation in vivo in addition to the transformation of fibroblasts. The v-mos gene product, termed p37mos, is a cytoplasmic protein recently shown to possess serine kinase activity in immune complexes. Autophosphorylation of the mos gene product is not necessary for its biological activity as exemplified by the protein HT1-MSV which lacks phosphoserine residues. A transcriptional regulatory property has been attributed to the v-mos gene product during infection, which may play an essential role in subsequent transformation.
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PMID:Functions of the mos oncogene family and associated gene products. 294 5


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