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 relative abundance of pp60c-src molecules associated with polyomavirus (Py) middle tumor antigen (MTAg) and the relative abundance of MTAg associated with pp60c-src in a variety of Py-transformed rat cells was determined by quantitative immunoblot analyses which detect pp60c-src or Py MTAg. The results demonstrate that approximately 5 to 10% of the total immunoprecipitable pp60c-src molecules in Py-transformed rat cells are stably associated with MTAg and have elevated protein kinase activities. In these same cells, it was found that approximately 10 to 15% of the detectable MTAg molecules are stably associated with pp60c-src. Other results presented in this report demonstrate that approximately 50 to 75% of the total MTAg-associated cellular tyrosine kinase activity potentially represents the enzymatic activity of pp60c-src, while the remaining 25 to 50% represents the activity of other cellular tyrosine kinases. Our results also show that most pp60c-src molecules associated with Py MTAg do not possess electrophoretic mobilities that are altered from those of pp60c-src molecules not associated with MTAg or pp60c-src molecules obtained from normal rodent cells.
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PMID:Analysis of middle tumor antigen and pp60c-src interactions in polyomavirus-transformed rat cells. 244 13

We have compared the level of phosphotyrosyl phosphatase activity in lysates from normal human colon mucosal cells and human colon carcinoma cells and analyzed the effect of incubating these cells with sodium orthovanadate, an inhibitor of phosphotyrosyl phosphatase activity, on the relative abundance of acid-stable phosphotyrosine and on in vitro protein kinase activity of pp60c-src. Additionally, we compared the effect of lysing these cells in buffer containing only nonionic detergents with RIPA buffer, which contains both sodium dodecyl sulfate and deoxycholate, on the in vitro kinase activity of pp60c-src. Our results show that the level of detectable phosphotyrosyl phosphatase activity in lysates derived from normal colon cells and colon carcinoma cells is very similar. Additionally, the abundance of acid-stable phosphotyrosine in these cells cultured in the absence or presence of vanadate is not significantly different. However, incubation of these cells with vanadate significantly stimulates the activity of pp60c-src derived from the normal colon cells in immune-complex kinase assays, while having no detectable effect on the activity of pp60c-src from the colon tumor cells. The in vitro protein kinase activity of pp60c-src derived from RIPA buffer lysates of colon carcinoma cells was found to be elevated five- to sevenfold when compared with pp60c-src from these same cells lysed in buffer containing only Nonidet-P 40 as a detergent. The type of lysis buffer did not effect the activity of pp60c-src from normal colon mucosal cells. These results provide additional evidence that the activity of pp60c-src may be regulated differently in colon carcinoma and normal colon mucosal cells.
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PMID:Analysis of pp60c-src tyrosine kinase activity and phosphotyrosyl phosphatase activity in human colon carcinoma and normal human colon mucosal cells. 244 18

The tyrosine-specific protein kinase activity of pp60c-src molecules obtained from RIPA buffer lysates of human colon tumor-derived cell lines is elevated over that found in lysates from normal human colon mucosa cells. The elevation of pp60c-src kinase activity in the lysates of the cultured colon tumor cells does not appear to be the result of pp60c-src overexpression suggesting that the specific activity of the pp60c-src phosphotransferase may be enhanced. Cell-free translation of c-src mRNA from colon tumor cells and normal colon mucosa cells yielded pp60c-src molecules with similar levels of in vitro protein kinase activity suggesting that pp60c-src kinase activity in these cells may be regulated differently at a post-translational level. Analysis of pp60c-src molecules from normal colon and colon carcinoma cells revealed that they possessed indistinguishable sites and quantities of phosphorylated serine and tyrosine residues and were not detectably complexed with other cellular proteins. The activation of pp60c-src kinase activity in the colon tumor cells is associated with an apparent increase in the turnover rate of tyrosine-phosphates within the carboxyl terminal portion of the pp60c-src molecules from these tumor derived cell lines.
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PMID:Analysis of pp60c-src in human colon carcinoma and normal human colon mucosal cells. 245 14

We have studied pp60c-src expression in the striatum, hippocampus, and cerebellum of the developing rat brain. In the striatum, pp60c-src protein kinase activity peaks during embryonic development and then declines in the adult. The peak activity occurs in the striatum on embryonic day 20 (E20) when it is 18- to 20-fold higher than the activity in fibroblasts and 4- to 5-fold higher than the activity in the striatum at E15 or in the adult striatum. In the hippocampal region, pp60c-src activity reaches a maximum shortly after birth but remains high throughout life. On postnatal day 2 (P2) the activity in the hippocampus is 9- to 13-fold higher than the activity in fibroblasts and twice as high as the activity in the hippocampus at E18. In the cerebellum, the kinase activity remains constant from E20 onward and is 6- to 10-fold higher than that observed in fibroblasts. The increase in pp60c-src kinase activity observed during the development of the striatum and hippocampus is due to an increase in the amount of pp60c-src protein and to an increase in the specific activity of the kinase. The increase in specific activity in these regions coincides with the peak periods of neurogenesis and neuronal growth. In the striatum, we have found that the increase in pp60c-src activity also parallels the increase observed in culture as embryonic striatal neurons differentiate. Taken together, our results are consonant with the idea that pp60c-src is the product of a developmentally regulated gene that is important for the differentiation and/or the continuing function of neurons.
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PMID:pp60c-src expression in the developing rat brain. 245 56

Differentiating rat neurons express high levels of the protooncogene product pp60c-src, a 60-kDa tyrosine kinase of unknown function encoded by c-src. pp60c-src was found to be concentrated at least 9-fold in membranes from a subcellular fraction of nerve growth cones, the motile tips of outgrowing neuronal processes. Indirect immunofluorescence staining of cultured chick retinal explants showed pp60c-src in neuronal growth cones and processes, with the antigen particularly concentrated in growth cones of long neurites. pp60c-src in growth cone membranes was an active tyrosine-specific protein kinase with elevated tyrosine-specific protein kinase activity and reduced electrophoretic mobility characteristic of the form of pp60c-src in central nervous system neurons. pp60c-src was present at lower levels in subcellular fractions from mature rat brain but synaptosomal membranes were not enriched. Preferential localization of an active form of pp60c-src in nerve growth cone membranes and persistence of pp60c-src in mature neurons suggest that this tyrosine kinase is important in growth cone-mediated neurite extension and synaptic plasticity.
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PMID:c-src gene product in developing rat brain is enriched in nerve growth cone membranes. 245 89

Lipocortin I is a 39-kilodalton membrane-associated protein that in A431 cells is phosphorylated on tyrosine in response to epidermal growth factor (EGF). We have used recombinant human lipocortin I as a substrate for several protein kinases and identified phosphorylated residues by a combination of peptide mapping and sequence analysis. Lipocortin I was phosphorylated near the amino terminus at Tyr-21 by recombinant pp60c-src. The same tyrosine residue was phosphorylated by polyoma middle T/pp60c-src complex, by recombinant pp50v-abl, and with A431 cell membranes by the EGF receptor/kinase. The primary site of phosphorylation by protein kinase C was also near the amino terminus at Ser-27. The major site of phosphorylation by adenosine cyclic 3',5'-phosphate dependent protein kinase was on the carboxy-terminal half of the molecule at Thr-216. These sites are compared to the phosphorylation sites previously located in the structurally related protein lipocortin II.
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PMID:Location of sites in human lipocortin I that are phosphorylated by protein tyrosine kinases and protein kinases A and C. 245 90

cdc2 is a catalytic subunit of a protein kinase complex, called the M-phase promoting factor, that induces entry into mitosis and is universal among eukaryotes. In HeLa cells, cdc2 is shown to be the most abundant phosphotyrosine-containing protein and its phosphotyrosine content is subject to cell-cycle regulation. One site of cdc2 tyrosine phosphorylation in vivo is selectively phosphorylated by pp60c-src in vitro.
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PMID:Human cdc2 protein kinase is a major cell-cycle regulated tyrosine kinase substrate. 246 72

We examined the expression, abundance, and protein kinase activity of pp60c-src in two different pairs of genetically indistinguishable cloned human neuroblastoma cell variants which display altered phenotypes as the result of conversion from a neuronal to a non-neuronal phenotype. The results demonstrate that cells which exhibit the neuroblastic (N-type) phenotype possess high levels of pp60c-src protein and that one of the two N-type cell lines is capable of expressing the neuronal-specific isoenzyme of pp60c-src. In contrast, cells which display the substrate-adherent (S-type) phenotype have low levels of pp60c-src protein and express exclusively the non-neuronal isoenzyme of pp60c-src. In all cells examined the abundance of pp60c-src was found to be proportional to the steady-state level of c-src RNA. In each case the protein kinase activity of pp60c-src was found to be proportional to the abundance of the protein and independent of the ratio of neuronal to non-neuronal species of pp60c-src.
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PMID:Coordinate alteration of pp60c-src abundance and c-src RNA expression in human neuroblastoma variants. 247 6

The product of the c-src proto-oncogene, pp60c-src, is phosphorylated at Ser-17 by cyclic AMP-dependent protein kinase A and at Ser-12 by calcium-phospholipid-dependent protein kinase C (when stimulated by 12-O-tetradecanoyl phorbol acetate). We tested the effects of Ser----Ala and Ser----Glu mutations at these sites in pp60c-src and in pp60c-src(F527) (a mutant whose transforming activities are enhanced by Tyr-527----Phe mutation) by transfecting single-, double-, and triple-mutant src expression plasmids into NIH 3T3 cells. Tryptic phosphopeptide analyses of the mutant proteins confirmed prior biochemical identifications of the phosphorylation sites and showed that neither separate nor coordinate mutations at Ser-12 and Ser-17 affected Tyr-416, Tyr-527, or Ser-48 phosphorylation or prevented mitosis-specific phosphorylations of either pp60c-src or pp60c-src(F527). Ser-12 mutation did not affect phosphorylation of the Ser-17-containing peptide, but mutation of Ser-17 significantly increased phosphorylation at Ser-12. Specific kinase activities (both with and without in vivo 12-O-tetradecanoyl phorbol acetate treatment) and the abilities of pp60c-src and pp60c-src(F527) to induce foci, transformed morphologies, and anchorage-independent growth were unaffected by any of the serine mutations. Thus, pp60c-src transforming activity in NIH 3T3 cells is relatively insensitive to phosphorylation at these sites, but there is a suggestion that Ser-17 phosphorylation may have a subtle regulatory effect.
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PMID:Mutation of amino acids in pp60c-src that are phosphorylated by protein kinases C and A. 247 54

The effects of butyrate-mediated differentiation of human colon carcinoma cells on the expression of src-related tyrosine protein kinases were analyzed. The results demonstrate that treatment of a variety of colon carcinoma cell lines with 2 mM sodium butyrate resulted in diminished population doubling rates, altered morphology, decreased anchorage-independent growth, and increased expression of colon epithelial differentiation marker enzymes such as alkaline phosphatase. In butyrate-treated cells, significantly diminished protein kinase activities and abundance of pp60c-src and p56lck were found to parallel the butyrate-induced phenotypic alterations. For the lck gene, the decreased levels in p56lck abundance were found to coincide with diminished levels of steady-state lck mRNAs. In contrast, treatments which arrested the growth of the colon carcinoma cells without inducing differentiation had no effect on the level of expression of these proteins. Furthermore, colon carcinoma cell lines which were found to be resistant to butyrate-induced differentiation showed no change in the kinase activity or abundance of either protein following butyrate treatment. These results indicate that the expression of several src-related kinases in human colon carcinoma can be influenced by the differentiation state of the cells.
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PMID:Alterations in the expression of pp60c-src and p56lck associated with butyrate-induced differentiation of human colon carcinoma cells. 247 6


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