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)

Insulin receptor was copurified from human placenta together with insulin-stimulated kinase activity that phosphorylates the insulin receptor on serine residues. Analysis of phosphorylated insulin receptor by two-dimensional tryptic peptide mapping showed that sites of insulin stimulated serine phosphorylation in the insulin receptor were recovered in the same peptides as those known to be phosphorylated on serine in vivo in response to insulin. This indicates that the serine kinase copurified with the insulin receptor represents a physiologically important enzyme involved in the insulin triggered serine phosphorylation of the insulin receptor in vivo.
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PMID:Characterization of sites of serine phosphorylation in human placental insulin receptor copurified with insulin-stimulated serine kinase activity by two-dimensional thin-layer peptide mapping. 246 5

Binding of tumor necrosis factor-alpha (TNF-alpha) to its receptor on U937 cells results in rapid and TNF dose-dependent phosphorylation of a cytosolic protein with an apparent molecular mass of 26,000 kDa (p26) and an isoelectric point of 5.6. Half-maximal phosphorylation of p26 was achieved at concentrations of 1.8 ng/ml and was detectable within 20 s of TNF-alpha treatment. p26 is phosphorylated exclusively at serine residues. p26 phosphorylation occurs at 37 degrees C as well as at 14 degrees C, indicating that internalization of the TNF receptor is not required for serine kinase activation. Dephosphorylation of p26 starts 10 min after TNF-induced phosphorylation, suggesting a possible regulatory function of this cytosolic protein within the post-TNF receptor signaling system. p26 is also phosphorylated upon treatment with lymphotoxin. In contrast, both interferon-gamma and lipopolysaccharide fail to induce p26 phosphorylation. Whereas phosphorylated p26 was detected in the TNF-sensitive breast cancer cell line CRL1500, other TNF-responsive tumor cell lines investigated lacked enhanced phosphorylation of p26 in response to TNF, indicating that the 26-kDa phosphoprotein (pp26) may be a cell type-specific second messenger molecule involved in TNF signal transduction in some, but not all, target cells. p26 is also phosphorylated in a subclone of U937 (U937.C27) that responds to TNF-alpha with differentiation, yet is resistant to TNF-alpha-mediated growth inhibition. In contrast, p26 is not phosphorylated in another U937 derivative (U937.G3) that is resistant to both TNF-alpha-induced growth arrest and differentiation, suggesting that pp26 may play a role in the TNF signaling pathway linked to differentiation processes rather than to growth control.
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PMID:Tumor necrosis factor signal transduction. Tissue-specific serine phosphorylation of a 26-kDa cytosolic protein. 253 51

The human immunodeficiency virus Rev protein is posttranslationally modified by a serine kinase activity present in the nucleus of the cell. Site-directed mutagenesis was used to identify the site of phosphorylation. Changing of serine residues 92 and 99 dramatically reduced Rev phosphorylation, suggesting that at least one, if not both, of these residues is the one recognized by the Rev-specific serine kinase. Similarly, a truncated Rev protein lacking the 25 carboxy-terminal amino acids was not phosphorylated. By using two independent assays, both the serine mutant proteins and the truncated form of Rev were found to be fully functional. Thus, phosphorylation and the 25 carboxy-terminal amino acids appear to be dispensable for protein function.
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PMID:Functional significance of phosphorylation to the human immunodeficiency virus Rev protein. 255 Jun 74

Insulin and the insulin-like growth factors (IGF) I and II are structurally related peptides that elicit a large number of similar biological effects in target cells. Three well-characterized receptor complexes bind one or more of these peptides with high affinity. Two of these receptors, denoted as type I, are ligand-activated tyrosine kinases with similar heterotetrameric alpha 2 beta 2 subunit structures which bind insulin or IGF-I, respectively, with highest affinity. Ligand-stimulated tyrosine autophosphorylation of these receptors further activates their intrinsic tyrosine kinase activities both in vitro and in intact cells. Rapid signal transduction follows such receptor autophosphorylation and tyrosine kinase activation, leading to increased serine phosphorylation of many cellular proteins and decreased serine phosphorylation of several others. Experiments in our laboratory have identified three distinct insulin-activated serine kinase activities in cell-free extracts that appear to account for the insulin-stimulated serine phosphorylation of the insulin receptor itself, ATP citrate lyase, and acetyl CoA carboxylase, respectively. A third receptor in this group binds IGF-I and II, lacks kinase activity and is denoted as type II IGF receptor. Amino acid sequences of this receptor deduced from isolated rat cDNA clones show a high degree of homology with those of the bovine cation-independent mannose 6-phosphate (Man-6-P) receptor. We demonstrated that these receptors are indeed identical. The IGF-II/Man-6-P receptor rapidly recycles between the cell surface membrane and intracellular membrane compartments, providing for the rapid uptake of both IGF-II and mannose 6-phosphate-linked lysosomal enzymes. Insulin action markedly increases the proportion of receptors in the plasma membrane and the uptake of bound ligands. We also observe that large amounts of the extracellular domain of the IGF-II/Man-6-P receptor are released into the serum of fetal, neonatal and adult rats. The biological role of this receptor in IGF-II function is yet to be determined.
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PMID:Multifunctional glycoprotein receptors for insulin and the insulin-like growth factors. 255 7

Treatment of Jurkat T-cells with anti-CD-3 monoclonal antibodies resulted in the rapid and transient activation of a serine kinase which utilized the microtubule-associated protein, MAP-2, as a substrate in vitro. The kinase was also activated on treatment of Jurkat cells with phytohaemagglutinin, but with a different time course. The activation of the MAP-2 kinase by anti-CD-3 antibodies was dose-dependent, with maximal activity observed at concentrations of greater than 500 ng/ml. Normal human E-rosette-positive T-cells also exhibited induction of MAP-2 kinase activity during anti-CD-3 treatment. The enzyme was optimally active in the presence of 2 mM-Mn2+; lower levels of activity were observed with Mg2+, even at concentrations up to 20 mM. The kinase was partially purified by passage over DE-52 Sephacel with the activity eluting as a single peak at 0.25 M-NaCl. The molecular mass was estimated to be 45 kDa by gel filtration. The activation of the MAP-2 kinase was probably due to phosphorylation of this enzyme as treatment with alkaline phosphatase diminished its activity. These data demonstrate that the stimulation of T-cells through the CD-3 complex results in the activation of a novel serine kinase which may be critically involved in signal transduction in these cells.
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PMID:Complexing of the CD-3 subunit by a monoclonal antibody activates a microtubule-associated protein 2 (MAP-2) serine kinase in Jurkat cells. 255 97

1. A protein kinase activity which is cAMP-independent, inhibited by the bioflavonoid quercetin and probably connected to the growth of mammary gland cells was isolated and partially purified from cytosol. 2. Another protein kinase activity was demonstrated in crude membranes of lactating mouse mammary gland. 3. By the use of several different synthetic peptides as a substrate, it was demonstrated that the cytosol enzyme was a serine kinase, while the membrane protein kinase activity was mainly due to tyrosine kinase.
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PMID:The difference between cytosol and membrane growth-related protein kinase activities in lactating mouse mammary gland. 274 6

Avian reticuloendotheliosis virus (REV-T) is the most virulent of all retroviruses, inducing an invariably fatal leukemia in chickens with a latent period of 7-10 days. Unlike avian cells transformed by other acutely transforming viruses, lymphoid cells transformed by REV-T are immortalized. Furthermore, in vitro derived, REV-T transformed cells which do not produce virus are tumorigenic and induce lethal reticuloendotheliosis when injected into histocompatible birds. Thus REV-T transforms its target cell both in vitro and in vivo. In addition this transformation is independent of any helper virus functions. Like other acute leukemia viruses, REV-T is replication-defective and must co-replicate with a reticuloendotheliosis associated virus (REV-A). During evolution, a substantial portion of its genome has been deleted and replaced with a host-derived genetic sequence, designated v-rel. Presumably, the v-rel oncogene was transduced from a normal turkey DNA locus, c-rel. There are 9 regions of homology between c-rel and v-rel, however, several differences exist between these genes, suggesting that transformation by REV-T results from the production of an altered v-rel protein. The v-rel sequence is distinct from other known oncogenes and encodes a 57-kDa phosphoprotein. In REV-T transformed cells, this pp57v-rel protein is localized in the cytoplasm. The product of the v-rel oncogene is present at a low level, representing only about 0.003% of total methionine-labelled protein. In addition, pp57v-rel is relatively stable, having an estimated half-life of 4-10 h. The v-rel protein when purified close to homogeneity is complexed with a 40-kDa cellular phosphoprotein in transformed lymphoid cells and possesses serine kinase activity. This review discusses the molecular aspects of transformation by REV-T in the context of other oncogene-encoded proteins.
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PMID:Transformation of avian lymphoid cells by reticuloendotheliosis virus. 282 14

The c-mos proto-oncogene exists as a maternal mRNA in mammalian oocytes, in that it has been shown to accumulate in mouse oocytes during the growth phase and to be present at high levels in fully grown oocytes. The function of c-mos during the subsequent development of the oocytes and embryos was examined by determining the fate of the oocyte c-mos mRNAs by in situ hybridization and Northern blot hybridization analysis. A substantial decrease in the levels of c-mos transcripts was observed in oocytes undergoing meiotic maturation. By the two-cell stage, levels of c-mos transcripts dropped to below the limits of detection using in situ hybridization. c-mos transcripts remained undectable through the blastocyst stage of embryogenesis. Analysis of meiotic maturation in vitro permitted finer temporal resolution of the initial drop in c-mos levels. Between approximately 7 and 17 h of culture, the amount of c-mos mRNA fell to 18-43% of the levels found in the fully grown oocyte. This interval corresponds to the progression of meiotic maturation from metaphase I to metaphase II. Our in vivo studies showed that ovulation per se is not the stimulus for the drop in c-mos transcript levels, since preovulatory metaphase II oocytes exhibited this decline to a degree comparable to that of ovulated metaphase II oocytes. The development specificity of c-mos transcript levels suggests a role of this putative serine kinase in the meiotic maturation of mammalian germ cells.
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PMID:Evidence for the involvement of the proto-oncogene c-mos in mammalian meiotic maturation and possibly very early embryogenesis. 284 Feb 83

Many retroviral oncogenes have been classified into one of several categories based on structure, enzymology and cellular localization. These genes originated from host cells and are probably derived from genes normally involved in the control of cell proliferation. The cellular counterparts of three oncogenes have been identified as a growth factor or growth factor receptor; related oncogenes include receptor-like membrane proteins which often express tyrosine kinase activity. These growth factor-related oncogenes are structurally and biochemically distinct from the membrane-associated ras gene family, which bind and hydrolyse GTP. Oncogenes localized primarily in the cytoplasm which probably have serine kinase activity, have also been identified. Although the structure and biochemistry of many oncogenes have been extensively studied, relatively little is known about the functional relationships of oncogene proteins within the cell. An opportunity to study such interaction is provided by the identification of a monoclonal antibody that neutralizes cellular ras proteins when microinjected into cells. It has been shown previously that the injected antibody inhibits the initiation of S-phase in NIH 3T3 cells. In the present study we injected this monoclonal antibody into NIH 3T3 cells transformed by a variety of oncogenes. The results show that transformation by three growth factor receptor-like oncogenes depends on c-ras proteins, while transformation by two cytoplasmic oncogenes appears to be independent of c-ras protein.
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PMID:Requirement for c-ras proteins during viral oncogene transformation. 293 16

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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