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

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that the proto-oncogene c-src plays a functional role in developing neurons, and in the mature nerve cells of higher vertebrates. The coelenterate Hydra represents the most primitive known organism possessing nerve cells. With Southern blot hybridizations we have demonstrated src-related sequences in Hydra. Antisera specific for the c-src gene product (pp60c-src) of birds and mammals precipitate a protein from Hydra cell extracts with a tyrosine-specific protein kinase activity. Studies of tissues and cells fractionated from a temperature sensitive mutant of Hydra which is depleted of interstitial (including nerve) cells at the non-permissive temperature, have indicated the src-like kinase of Hydra to be preferentially expressed in nerve cells. The high conservation of structural features and of the expression pattern indicates a basic function for pp60c-src in neurons.
...
PMID:Preferential expression of a pp60c-src related protein tyrosine kinase activity in nerve cells of the early metazoan Hydra (Coelenterates). 247 83

The physiological roles, precise locations, and relevant targets of the 60 kD protein-tyrosine kinase encoded by viral and cellular src genes p60src are not known, despite intensive study. We describe recent work that bears upon these unresolved problems: (i) p60c-src is phosphorylated during mitosis on threonine and serine residues by the protein kinase encoded by the mammalian homologue of cdc2, suggesting that c-src may contribute to the phenotype of mitotic cells; (ii) multiple regions in the amino-terminal portion of p60src are required for its proper intracellular localization--a short signal for myristylation and signals for association with cytoplasmic granules and with perinuclear and plasma membranes; and (iii) regions (called SH3 and SH2) upstream of the kinase domain modulate the behavior of p60src in complex ways, with some mutations in SH2 rendering p60 host-dependent for transformation. The latter mutants may prove to be powerful tools for identifying proteins that modify or serve as targets for src-encoded protein-tyrosine kinases.
...
PMID:Function, location, and regulation of the src protein-tyrosine kinase. 248 25

Maturation-promoting factor (MPF) is a cell cycle control element able to cause metaphase when injected into amphibian oocytes or when incubated with nuclei in a cell-free system. Highly purified MPF consists of a complex between a 34K (K = 10(3) Mr) serine/threonine protein kinase, identified as a Xenopus homolog of the cdc2+ gene product, p34cdc2, and a 45K substrate, identified as a Xenopus B-type cyclin. p34cdc2 is also present in purified preparations of chromatin-derived growth-associated histone H1 kinase from Novikoff hepatoma cells. p34cdc2 is active when dephosphorylated and inactive when phosphorylated during oocyte meiotic cell cycles and in mitotic cell cycles following egg activation. Analysis of the substrate specificity of p34cdc2 indicates a consensus sequence for phosphorylation of (K/R)S/TP(X)K/R. Among substrates identified with this consensus are histone H1 and the pp60c-src proto-oncogene, which is known to be activated and phophorylated in mitosis. MPF injection into oocytes activates ribosomal protein S6 kinase II, which is also a lamin kinase. The mechanism of activation is indirect, possibly involving the c-src proto-oncogene. Continued analysis of regulation of MPF activation/inactivation and characterization of substrates for phosphorylation will have important implications for cell cycle and cell growth control.
...
PMID:Maturation-promoting factor and the regulation of the cell cycle. 269 38

Human cell lines with neuronal and neuroendocrine features were examined for their expression of pp60c-src, the cellular homolog of the transforming gene product pp60v-src of Rous sarcoma virus. Four neuroblastoma (LA-N-5, SH-SY5Y, Paju, and SK-N-MC) and three small-cell lung carcinoma (U-2020, U-1690, and U-1285) cell lines were selected on the basis of their stage of neurocrine differentiation, as determined by the expression of neuron-specific enolase. In an immune complex protein kinase assay, all seven cell lines displayed c-src kinase activity which was considerably higher than that found in nonneurocrine cells (human diploid fibroblasts, glioma, and non-small cell lung carcinoma cell lines). Furthermore, the c-src kinase activity, as determined by autophosphorylation or phosphorylation of an exogenous substrate, enolase, correlated with the stage of neurocrine differentiation. There was an approximately 30-fold difference in c-src kinase autophosphorylation activity between the cell lines representing the highest and lowest stages of neurocrine differentiation. A similar variation was found in the steady-state levels of the c-src protein of these cell lines. Highly differentiated neuroblastoma cells expressed two forms of the src protein. Digestion by Staphylococcus aureus V8 protease did reveal structural diversity in the amino-terminal ends of these c-src molecules. In summary, we found a clear correlation between c-src kinase activity and the stage of neuronal and neuroendocrine differentiation. Thus, the phenotypic similarity between neurons and neuroendocrine cells includes high c-src expression.
...
PMID:Expression of c-src in cultured human neuroblastoma and small-cell lung carcinoma cell lines correlates with neurocrine differentiation. 283 Apr 84

Twelve independent isolates of avian sarcoma viruses (ASVs) can be divided into four groups according to the transforming genes harbored in the viral genomes. The first group is represented by viruses containing the transforming sequence, src, inserted in the viral genome as an independent gene; the other three groups of viruses contain transforming genes fps, yes or ros fused to various length of the truncated structural gene gag. These transforming sequences have been obtained by avian retroviruses from chicken cellular DNA by recombination. The src-containing viruses code for an independent polypeptide, p60src; and the representative fps, yes and ros-containing ASVs code for P140/130gag-fps, P90gag-yes and P68gag-ros fusion polypeptides respectively. All of these transforming proteins are associated with the tyrosine-specific protein kinase activity capable of autophosphorylation and phosphorylating certain foreign substrates. p60src and P68gag-ros are integral cellular membrane proteins and P140/130gag-fps and P90gag-yes are only loosely associated with the plasma membrane. Cells transformed by ASVs contain many newly phosphorylated proteins and in most cases have an elevated level of total phosphotyrosine. However, no definitive correlation between phosphorylation of a particular substrate and transformation has been established except that a marked increase of the tyrosine phosphorylation of a 34,000 to 37,000 dalton protein is observed in most ASV transformed cells. The kinase activity of ASV transforming proteins appears to be essential, but not sufficient for transformation. The N-terminal domain of p60src required for myristylation and membrane binding is also crucial for transformation. By contrast, the gag portion of the FSV P130gag-fps is dispensable for in vitro transformation and removal of it has only an attenuating effect on in vivo tumorigenicity. The products of cellular src, fps and yes proto-oncogenes have been identified and shown to also have tyrosine-specific protein kinase activity. The transforming potential of c-src and c-fps has been studied and shown that certain structural changes are necessary to convert them into transforming genes. Among the cellular proto-oncogenes related to the four ASV transforming genes, c-ros most likely codes for a growth factor receptor-like molecule. It is possible that the oncogene products of ASVs act through certain membrane receptor(s) or enzyme(s), such as protein kinase C, in the process of cell transformation.
...
PMID:Avian sarcoma viruses. 283 47

We have transfected the polyoma middle T oncogene into an immortal murine melanocyte cell line, Mel-ab. This highly pigmented line is phorbol ester (TPA) dependent for in vitro growth, suggesting activation and/or down regulation of Protein Kinase C (PKC) is essential for mitogenesis. Moreover, cells of this line do not form tumours when injected subcutaneously into immunocompetent or immunoincompetent mice. Here we show that PyMT alone is sufficient to produce TPA-independence and transformation to the tumourigenic state in transfected Mel-ab cells. Western blot analysis shows that middle T overcomes the TPA requirement by a mechanism independent of PKC down regulation though this does appear to occur when Mel-ab cells are grown continuously in TPA. These results suggest that PyMT is not exerting its transforming effect by PKC down regulation, but conceivably at some later stage of second messenger signalling, possibly through PyMT-c-src protein kinase activity.
...
PMID:Polyoma middle T abrogates TPA requirement of murine melanocytes and induces malignant melanoma. 285 52

We have evaluated the level of pp60c-src protein kinase activity in a variety of human tumor tissues and human tumor cell lines, and have estimated the abundance of the c-src protein in several of these tissues and cell lines. All cell lines derived from tumors of neuroectodermal origin that express a neural phenotype were found to possess c-src molecules with high levels of tyrosine-specific protein kinase activity. In contrast, cell lines derived from tumors of neuroectodermal origin that do not express neural characteristics, such as glioblastomas and melanomas, were found to have pp60c-src molecules with low levels of protein kinase activity. A similar pattern was observed when we analyzed the activity of c-src molecules extracted directly from corresponding tumor tissues. Analysis of human tumor cell lines derived from tissues other than those of neuroectodermal origin revealed that pp60c-src protein kinase activity was low in most cases. Exceptions to this observation were all rhabdomyosarcoma, osteogenic sarcoma, Ewing's sarcoma, and colon carcinoma lines tested. Comparison of pp60c-src kinase activity in normal skeletal muscle and rhabdomyosarcoma tissue and in normal breast tissue and breast adenocarcinoma tissue revealed that pp60c-src kinase activity was specifically elevated in the tumor tissues in both cases. However, the amount of pp60c-src protein in both normal and tumor tissues was found to be similar. These observations suggest that increases in the specific activity of the pp60c-src phosphotransferase in some rhabdomyosarcomas and breast carcinomas may be a characteristic acquired during the malignant transformation of the cells that is retained in cell lines established from these tumors.
...
PMID:Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues. 309 83

We introduced two mutations into the carboxy-terminal regulatory region of chicken pp60c-src. One, F527, replaces tyrosine 527 with phenylalanine. The other, Am517, produces a truncated pp60c-src protein lacking the 17 carboxy-terminal amino acids. Both mutant proteins were phosphorylated at tyrosine 416 in vivo. The specific activity of the Am517 mutant protein kinase was similar to that of wild-type pp60c-src whereas that of the F527 mutant was 5- to 10-fold higher. Both mutant c-src genes induced focus formation on NIH 3T3 cells, but the foci appeared at lower frequency, and were smaller than foci induced by polyoma middle tumor antigen (mT). The wild-type or F527 pp60c-src formed a complex with mT, whereas the Am517 pp60c-src did not. The results suggest that one, inability to phosphorylate tyrosine 527 increases pp60c-src protein kinase activity and transforming ability; two, transformation by mT involves other events besides lack of phosphorylation at tyrosine 527 of pp60c-src; three, activation of the pp60c-src protein kinase may not be required for transformation by the Am517 mutant; and four, the carboxyl terminus of pp60c-src appears to be required for association with mT.
...
PMID:Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain. 310 27

We have compared in different human neuroblastoma cell lines and human glioblastoma cells the expression level, structure, and tyrosine-specific protein kinase activity of pp60c-src. Our results show that not all human neuroblastoma cell lines express pp60c-src molecules with amino-terminal structural alterations. In neuroblastoma cells which possess pp60c-src with altered gel migration, the diminished polyacrylamide gel mobility of pp60c-src was found not to be dependent upon amino-terminal phosphorylations since extensive treatment of these molecules with phosphatase did not significantly change their gel migration properties. Similar differences in gel migration were observed when RNA from the various neuroblastoma and glioblastoma cells was translated in vitro using either rabbit reticulocyte or wheat germ lysates. White the level of c-src mRNA in the different cells analyzed was found to be similar, the abundance of pp60c-src in these same cells was found to vary by as much as 12-fold. This suggests that the abundance of pp60c-src in human neuroendocrine tumors is regulated through post-transcriptional and/or post-translational events which may be related to the stage of neuronal differentiation of the cells. Based upon determination of pp60c-src abundance by immunoblot analysis, we demonstrate that pp60c-src molecules derived from human neuroblastoma and glioblastoma cells have very similar in vitro protein kinase activities.
...
PMID:Analysis of the c-src gene product structure, abundance, and protein kinase activity in human neuroblastoma and glioblastoma cells. 314 45

We have determined the total coding sequence of human c-yes, a non-receptor type protein-tyrosine kinase gene, and found that the c-yes gene closely resembles the c-src gene. Recently, two new genes, syn and lyn, were found to encode proteins closely related to the yes product. In addition, we also determined the partial sequence of fgr. These genes together with lck reported by two American groups have very closely related structures and are thought to compose a closely related group of non-receptor type protein-tyrosine kinases. Partial analysis of the structures of these genes indicated that they have identical splicing junctions at all sites so far examined. On the other hand, the erbB-1/EGF (epidermal growth factor) receptor gene and the erbB-2/neu gene have completely different splicing junctions from those of the above gene group even in the kinase domain, although these genes also have protein kinase activity specific for tyrosine residues and the erbB-1 and -2 genes share splicing sites. These results suggest that the genes of the group of six non-receptor type kinases and those of the erbB-1 and erbB-2 gene group are descendants evolved by duplication of two distinct ancestor genes and are members of two distinct multi-gene families. The genes coding for protein kinases may be members of a super-family including multiple distinct gene families.
...
PMID:Nakahara memorial lecture. Non-receptor type protein-tyrosine kinases closely related to src and yes compose a multigene family. 333 5


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---