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)

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

Polyoma virus can transform the growth properties of rodent cells grown in culture and form tumours in susceptible animals, an activity largely due to one of the virus-encoded proteins, called middle T. Middle T has an associated tyrosine-specific protein kinase activity in vitro and interacts with cellular membranes, but the biochemical basis of its ability to transform remains unclear. Although there is some correlation between the transforming activity of different polyoma virus mutants and their ability to accept phosphate on tyrosine in middle T in the in vitro kinase reaction, the abundance of phosphotyrosine in protein is not elevated in polyoma virus-transformed cells and no cellular substrates for the putative kinase have been identified. It is also not yet known whether the tyrosine kinase of middle T is an intrinsic activity of the protein itself or the property of an associated enzyme. The experiments described here indicate that a fraction of middle T forms a stable complex with pp60c-src, the product of a cellular oncogene, and lead us to propose that the middle T associated kinase at least in part is a property of pp60c-src rather than middle T itself.
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PMID:Polyoma virus transforming protein associates with the product of the c-src cellular gene. 630 24

We have recently proposed that the transforming protein of polyoma virus, middle-T antigen, forms a complex with pp60c-src. Here we provide additional evidence for the existence of the complex using both monoclonal antibodies specific for middle-T and antibodies raised against synthetic peptides corresponding to sequences from both middle-T and pp60c-src. The complex was retained during partial purification of middle-T and was stable to incubation under various conditions. A survey of a number of mutants of middle-T antigen showed that there was a complete correlation between the ability of middle-T to accept phosphate in the in vitro kinase reaction and the presence of a middle-T: pp60c-src complex. This result is in accord with our hypothesis that middle-T itself is not a protein kinase but rather that pp60c-src phosphorylates middle-T. All mutant forms of middle-T antigen capable of transformation had associated pp60c-src. The middle-T of two non-transforming mutants (hr-t mutants) did not have associated pp60c-src, whereas other non-transforming middle-T species did associate with pp60c-src. We propose that the complex plays an essential role in transformation by polyoma virus, but that the existence of the complex per se may not be sufficient.
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PMID:The complex of polyoma virus middle-T antigen and pp60c-src. 632 77

Serum from Rous sarcoma virus tumor-bearing rabbits immunoprecipitated from extracts of the freshwater sponge Spongilla lacustris a tyrosine-specific protein kinase with characteristics similar to the chicken pp60c-src kinase activity. An immune competition assay confirmed the relationship between the protein from sponges and viral pp60v-src.
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PMID:Cellular src gene product detected in the freshwater sponge Spongilla lacustris. 633 May 36

An endogenous protein of human cells pp60c-src, which is closely related to the product of the transforming gene of Rous sarcoma virus, pp60v-src, has been quantitated by measuring its enzymatic activity in an immunoglobulin G protein kinase assay. The influence of normal developmental processes on pp60c-src expression was assessed by comparative analysis of various adult and fetal human tissues. The maximal difference detected was a 2- to 3-fold-enhanced activity in fetal muscle compared with adult muscle. Organ-specific variations in the enzyme level were observed. Highest activity was found in brain, followed by kidney, lung, muscle, and connective tissue. Since overexpression of the cellular counterparts of viral-transforming genes may play a role in carcinogenesis, pp60c-src kinase was measured in nine spontaneous human sarcomas and 21 mammary carcinomas. Compared with the respective normal tissues and human diploid fibroblasts, 4- to 20-fold-enhanced activities were observed in one-third of the sarcomas and carcinomas. The remainder showed no or insignificantly elevated activity. The enzymes from normal and malignant tissues were indistinguishable from the virus-coded enzyme with respect to specificity for divalent cations and a predominance of phosphorylation in tyrosine. Patients carrying tumors with high pp60c-src protein kinase activity did not develop kinase-reactive antibodies against pp60c-src or pp60v-src.
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PMID:Expression of pp60c-src protein kinase in adult and fetal human tissue: high activities in some sarcomas and mammary carcinomas. 640 27

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

The normal cellular protein pp60c-src is a tyrosine-specific protein kinase that is homologous to the transforming protein of Rous sarcoma virus (RSV) but its function is unknown. The expression of pp60c-src in chick and human embryonic tissues was monitored by the immune complex protein kinase assay, Western transfer analysis, and immunocytochemical staining at the light microscope level. pp60c-src kinase was expressed in the head and trunk regions of the chick embryo at all stages of development examined; however, expression increased significantly during the major period of organogenesis (Hamburger and Hamilton stages 21 to 32). Western transfer analysis showed that the amount of pp60c-src protein increased in parallel with the increase in kinase activity. Highest levels of pp60c-src kinase were present in the neural tube, brain, and heart of the stage 32 chick embryo. Lower levels of activity were found in eye, limb bud, and liver. Immunocytochemical staining of the neural tube region and heart of the chick confirmed the results of biochemical analysis and showed immunoreactive pp60c-src distributed throughout the neural tube and heart. The distribution of pp60c-src kinase in human fetal tissues was similar to that in the chick embryo; elevated levels of pp60c-src kinase were present in cerebral cortex, spinal cord, and heart, but all other tissues examined expressed some pp60c-src kinase. The results of our studies suggest that pp60c-src plays a fundamental role in an aspect of cellular metabolism that is particularly important in electrogenic tissues.
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PMID:pp60c-src Kinase is in chick and human embryonic tissues. 642 52

Tyrosine-specific protein kinases from normal tissue have been studied using synthetic peptides as substrate. Spleen had much higher activity of the enzyme in the particulate fraction than any other normal tissue (except purified T lymphocytes). The tyrosine protein kinase from the particulate fraction of rat spleen was partially purified and characterized. The kinase could phosphorylate src-related as well as unrelated peptides and casein at tyrosine residues. The enzyme in the membrane seemed to have somewhat different substrate specificity than the solubilized, partially purified enzyme. Serum containing antibody to pp60v-src did not precipitate the kinase; however, the protein kinase could phosphorylate the heavy chain of IgG from TBR serum (but not from normal serum). The possible relationship of the tyrosine-specific protein kinase of spleen with pp60c-src and other tyrosine-specific protein kinases is discussed.
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PMID:Tyrosine-specific protein kinases of normal tissues. 643 59

The endogenous cellular oncogene products, pp60c-src, exhibits a protein kinase activity, but is itself a phosphoprotein. Based on the assumption that pp60c-src might play a role in the control of cell proliferation, we have studied its behaviour as a substrate for phosphorylation known to occur when quiescent, serum-deprived cells are stimulated to enter cell cycle following addition of either serum, platelet-derived growth factor or the phorbol ester derivative, 12-O-tetradecanoyl-phorbol-13-acetate. For this purpose a partial purification of pp60c-src on DEAE ion-exchange chromatography was combined with immune precipitation. A 2-4-fold increase in serine phosphorylation of pp60c-src was consistently observed after stimulation of quiescent cells to growth.
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PMID:pp60c-src is a substrate for phosphorylation when cells are stimulated to enter cycle. 643 65

Recently, we reported that curcumin (diferuloylmethane) inhibits the growth of several different kinds of tumor cells. In order to investigate the mechanism of this inhibition, we examined the effects of curcumin on different protein kinases: highly purified protein kinase A (PkA), protein kinase C (PkC), protamine kinase (cPK), phosphorylase kinase (PhK), autophosphorylation-activated protein kinase (AK) and pp60c-src tyrosine kinase. While all kinases tested were inhibited by curcumin, only PhK was completely inhibited at relatively lower concentrations. At around 0.1 mM curcumin, PhK, pp60c-src, PkC, PkA, AK, and cPK were inhibited by 98%, 40%, 15%, 10%, 1%, and 0.5%, respectively. Lineweaver-Burk plot analysis indicated that curcumin is a non-competitive inhibitor of PhK with a Ki of 0.075 mM. Overall, our results indicate that curcumin is a potent and selective inhibitor of phosphorylase kinase, a key regulatory enzyme involved in the metabolism of glycogen. This has important implications for the anti-proliferative effects of curcumin.
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PMID:Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase. 751 Nov 11


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