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)

Our recent studies with cell mutants indicate that a cascade shared by the epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) signals exists in NRK cells and mediates oncogenic signals induced by many oncogenes (A. Masuda, S. Kizaka-Kondoh, H. Miwatani, Y. Terada, H. Nojima, and H. Okayama, New Biol. 4:489-503, 1992). We have employed the antisense RNA technique to investigate possible involvement of Raf-1 kinase in this signal transduction cascade. NRK cell clones highly reduced in the Raf-1 production are generated by the expression of a c-raf-1 antisense RNA. They have no apparent growth defects and retain proper mitotic responses to growth factors but are refractory to transformation by EGF or PDGF plus transforming growth factor beta, v-erbB, v-fms, v-K-ras, v-mos, v-fos, v-src, simian virus 40 large T, and polyomavirus middle T but not by v-raf or adenovirus E1A. These results not only support our model for the oncogenic signal cascade but also lead to the conclusion that Raf-1 protein kinase is a downstream component of this oncogenic signal cascade shared by EGF and PDGF.
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PMID:Raf-1 protein kinase is an integral component of the oncogenic signal cascade shared by epidermal growth factor and platelet-derived growth factor. 140 83

The influences of protein kinase inhibitors, K-252a and staurosporine, on the neurotrophic effects of epidermal growth factor (EGF) were investigated in dissociated cell cultures of the hippocampus and cerebellum of fetal rats. Addition of 1 ng/ml EGF enhanced the survival of cultured neurons of both brain regions. Both K-252a (10-200 nM) and staurosporine (1-100 nM) blocked the survival-promoting effects of EGF in a concentration-dependent manner. These results suggest that activation of protein kinase(s) is involved in the neurotrophic effects of EGF.
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PMID:Neurotrophic effects of epidermal growth factor on cultured brain neurons are blocked by protein kinase inhibitors. 143 24

An underinvestigated aspect of the mitogenic and cell regulatory actions of vanadium is the regulation of gene expression. Among the fifteen cellular genes studied in cultured mouse C127 cells, vanadium (as 10 microM sodium vanadate) increased levels of mRNA of the actin and c-Ha-ras to four times control values. These increases represented de novo synthesis of mRNA, since they were inhibited by actinomycin D. Vanadate did not increase mRNA corresponding to c-src, c-mos, c-myc, p53, HSP70, pODC or RB genes, and expression of c-erb A, c-erb B, c-sis and c-fes genes was undetectable whether vanadium was present or not. Expression of a third gene affected by vanadium, c-jun, was augmented by addition of a reductant or oxidant together with the vanadate. Addition of NADH (marginally effective on its own) or H2O2 (effective alone) dramatically enhanced the effect of vanadate on c-jun gene expression. Catalase inhibited the effect of NADH partly. The vanadate-stimulated expression of actin and c-Ha-ras mRNA were unaffected by oxidants, reductants, metal chelators, or anti-oxidant enzymes. Evidently vanadate acts by two separate mechanisms on these two categories of genes. The alternate hypothesis that the actions of vanadate on actin and c-Ha-ras were mediated by a protein kinase cascade was inconsistent with the following observations. Neither insulin nor epidermal growth factor increased mRNA levels of c-Ha-ras or actin gene. Neither genistein (a tyrosine kinase inhibitor) nor pretreatment with 12-O-tetradecanoylphorbol-13-acetate blocked the actions of vanadate on these genes. Clearly the biological actions of vanadium depend in part on altered expression of genes. Since two of the genes are proto-oncogenes, this mechanism is potentially relevant to the mitogenic responses of cells to vanadium.
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PMID:Vanadate-induced gene expression in mouse C127 cells: roles of oxygen derived active species. 143 69

A number of molecules have recently been described that effect the correct transport and assembly of cytoplasmically synthesized proteins to cellular membranes. To identify proteins that bind or modify other proteins during the process of membrane translocation, we developed a yeast selection scheme that employs the yeast transcriptional activator GAL4. This selection facilitates the isolation of cDNAs that encode proteases and binding proteins for known target peptide sequences. We report the isolation of an Arabidopsis cDNA encoding a polypeptide that can interact with the amino terminus of a ligh-harvesting chlorophyll a/b-binding protein (LHCP), a cytoplasmically synthesized protein that is integral to the chloroplast thylakoid membrane. The cDNA was selected in yeast from an Arabidopsis expression library for its ability to inhibit a transcriptional activator GAL4-LHCP fusion protein, but not inhibit native GAL4 protein. The LHCP amino-terminal sequences included in the fusion protein are known to regulate LHCP biogenesis and function. The Arabidopsis cDNA encodes a 595-amino acid protein with at least two functional domains, one with similarity to the family of protein-serine/threonine kinases and another that contains an epidermal growth factor repeat. The identification of an EGF repeat in Arabidopsis indicates that the motif is conserved between the plant and animal kingdoms. Hybridization studies indicate that this gene is likely to be present in other genera of plants. Its mRNA is detected in green leaves but not in other plant tissues or in etiolated plants. The specificity in yeast and the expression pattern in plants together are suggestive of a role for this protein kinase in the assembly or regulation of LHCP.
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PMID:An Arabidopsis serine/threonine kinase homologue with an epidermal growth factor repeat selected in yeast for its specificity for a thylakoid membrane protein. 143 3

As detected by coimmunoprecipitation from PC12 cells, NGF induces rapid association between ERK1 (a growth factor-activated serine/threonine protein kinase) and gp140prototrk NGF receptors. In contrast, no such association is found with the closely related ERK2. Anti-trk immunocomplexes generated from NGF-treated cells also contain protein kinase activity that shares many properties with soluble ERK1. The association of both ERK1 protein and ERK-like kinase activity with gp140prototrk is maximal by 5 min of NGF treatment, persists for approximately 1 hr, and subsequently declines by 18 hr. Treatment with either basic fibroblast growth factor, epidermal growth factor, or orthovanadate also leads to association of ERK1 with gp140prototrk without tyrosine phosphorylation of the latter. The interaction between ERK1 and gp140prototrk may prove relevant to the NGF mechanism.
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PMID:NGF and other growth factors induce an association between ERK1 and the NGF receptor, gp140prototrk. 146 7

Recent biochemical studies have suggested that apoptotic cell death is the molecular mechanism underlying the degeneration of ovarian follicles during atresia. Using a sensitive autoradiographic method for the detection of DNA fragmentation, we studied apoptosis in ovarian granulosa cells or intact follicles placed in serum-free culture as model systems to elucidate the hormonal regulation of atresia. Immature rats (25 days old) were primed for 2 days with 10 IU equine CG to induce a homogeneous population of mature preovulatory follicles. Granulosa cells isolated from these follicles contained predominantly intact high mol wt DNA. However, a time-dependent, spontaneous onset of internucleosomal DNA fragmentation characteristic of apoptotic cell death occurred in granulosa cells during culture. Treatment of granulosa cells with epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), or basic fibroblast growth factor (bFGF) inhibited the spontaneous onset of apoptotic DNA cleavage found during culture by 40-60%. In contrast, insulin-like growth factor I, insulin, TGF beta and tumor necrosis factor-alpha were ineffective. Likewise, activation of the protein kinase A or C pathways with forskolin or phorbol 12-myristate 13-acetate, respectively, did not prevent the onset of DNA fragmentation, although inclusion of a tyrosine kinase inhibitor (genistein) completely blocked the ability of EGF, TGF alpha, and bFGF to suppress apoptosis in granulosa cells. Similar to cultured granulosa cells, a spontaneous onset of apoptosis was also observed to occur in isolated preovulatory follicles during culture. Furthermore, treatment of follicles with EGF or bFGF inhibited the spontaneous initiation of apoptosis, and the suppressive effects of these growth factors were also attenuated by co-treatment with genistein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Epidermal growth factor and basic fibroblast growth factor suppress the spontaneous onset of apoptosis in cultured rat ovarian granulosa cells and follicles by a tyrosine kinase-dependent mechanism. 148 Jan 80

Treatment of quiescent Swiss 3T3 mouse fibroblasts with bombesin resulted in a rapid 6-8-fold stimulation of cytosolic Ser/Thr kinase activities toward the S6 peptide (RRLSSLR), myelin basic protein (MBP), and the G peptide (SPQPSRRGSESSEE). Anion exchange Mono Q chromatography resolved multiple S6 peptide- and G peptide kinase activities and two MBP kinase peaks. Both MBP- and several S6 peptide kinase peaks could be inactivated by PCSL (PP2A2) phosphatase action. This indicates that the bombesin-induced activation of these enzymes is mediated by a Ser/Thr phosphorylation event. The S6 peptide kinases as well as the two MBP kinases stimulated in response to bombesin are similar to those activated by epidermal growth factor in Swiss 3T3 fibroblasts which suggests that the early events of the signal transduction pathway mediated by these growth factors in Swiss 3T3 cells may converge in the activation of common Ser/Thr kinases. Bombesin, which acts as a sole mitogen for Swiss 3T3 fibroblasts, also produced a several-fold increase in the kinase activity toward the RRREEESEEE peptide, a specific substrate for CK-2. This kinase activity was heparin-sensitive and also measurable with the G peptide (SPQPSRRGSESSEE) and GS-1 peptide (YRRAAVPPSPSPSLSRHSSPHQSEDEE), which contain consensus sequences for phosphorylation by CK-2. The bombesin-stimulated CK-2 activity could not be measured in whole cytosols but was revealed by the anion exchange chromatography step. The activation of CK-2 was not reversed by PCSL phosphatase action. The implication of CK-2 in the signal transduction pathway of bombesin is discussed.
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PMID:Rapid stimulation of Ser/Thr protein kinases following treatment of Swiss 3T3 cells with bombesin. Involvement of casein kinase-2 in the signaling pathway of bombesin. 157 10

High resolution two-dimensional gel electrophoresis was used to analyze the signal transduction pathways of tumor necrosis factor (TNF-alpha) and interleukin 1 (IL-1 alpha and -beta) in human fibroblasts. Approximately 450 discrete radioactive spots were electrophoretically resolved from cytosolic extracts of cells prelabeled with 32P. At least 63 of these polypeptides exhibited significant and concordant phosphorylation or dephosphorylation in response to TNF or IL-1, despite the fact that different receptors are involved. Most of these changes concerned serine/threonine residues although enhanced tyrosine phosphorylation of several polypeptides was also observed. Phosphorylation patterns induced by a number of other agonists were compared with the patterns induced by IL-1 and TNF. These included activators of protein kinases C and A, bradykinin (a stimulator of inositol phospholipid hydrolysis), epidermal growth factor, heatshock, and mellitin (an activator of phospholipase A2). Although each of these agonists induced changes resulting in a distinct pattern of protein phosphorylation, none of these patterns had significant homology with that induced by IL-1 and TNF. Other assays were performed to verify the involvement of specific kinases. Collectively, these data indicate that IL-1 and TNF activate multiple protein kinases viz. a kinase(s) which activates microtubule-associated protein 2 (MAP-2) kinase, a kinase that phosphorylates the cap-binding protein, and a possibly novel serine/threonine protein kinase.
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PMID:Interleukin 1 and tumor necrosis factor activate common multiple protein kinases in human fibroblasts. 165 Mar 57

Two closely related members (mouse NUR 77 and rat NGFI-B) of the serum-inducible "early intermediate" gene family are nuclear hormone receptors containing zinc fingers of the cys2-cys2 type. This paper describes the complementary DNA cloning of the human equivalent of the NUR 77/NGFI-B genes isolated from LS-180 colon adenocarcinoma cells and named the ST-59 gene. ST-59 RNA expression was shown to be rapidly and transiently induced by fetal calf serum. To a lesser extent, epidermal growth factor could induce ST-59 RNA expression, but nerve growth factor, insulin-like growth factor, and fibroblast growth factor were ineffective. ST-59 receptor induction by serum was greatly amplified by cycloheximide and could be detected in actively growing LS-180 cells. The serum induction of RNA expression in these cells could be augmented by treatment with phorbol esters (10(-5) M), forskolin (10(-5) M), and 8-bromo cyclic AMP (4 x 10(-3) M). These results suggest that at least two signal pathways (protein kinase C and protein kinase A) participate in the ST-59 gene mRNA induction.
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PMID:Phorbol ester, forskolin, and serum induction of a human colon nuclear hormone receptor gene related to the NUR 77/NGFI-B genes. 165 Nov 1

The effects of epidermal growth factor (EGF) on basal 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) receptor level and on parathyroid hormone (PTH)-induced 1,25-(OH)2D3 receptor up-regulation were studied in the phenotypically osteoblastic cell line UMR 106. EGF in concentrations exceeding 0.1 ng/ml reduced the number of 1,25(OH)2D3 binding sites without changing the binding affinity. Maximal reduction was 30% at about 1 ng/ml. This reduction was independent of a change in cAMP content. EGF dose-dependently attenuated both PTH-induced 1,25(OH)2D3 receptor up-regulation and PTH-stimulated cAMP production, without an effect on the ED50 of the PTH effects. For both PTH responses the IC50 and the maximal effective dose were similar, 0.1 ng/ml and 1 ng/ml EGF, respectively. Reduction was first seen at 0.01 ng/ml EGF. At this concentration, EGF reduced PTH-stimulated 1,25-(OH)2D3 receptor binding without an inhibition of the cAMP response. Time-course studies with 1 ng/ml EGF revealed that at 2 h preincubation EGF reduced the heterologous up-regulation by PTH, and maximal inhibition was seen after 4 h. In contrast, PTH-stimulated cAMP production was just significantly inhibited only after 6 h, with 60% inhibition after 24 h preincubation. The effects of prostaglandin E2 and forskolin on both 1,25(OH)2D3 binding and cAMP production were inhibited in a similar fashion. On the other hand, dibutyryl cAMP- and 3-isobutyl-1-methylxanthine-stimulated 1,25(OH)2D3 binding were not affected by EGF. Taken together, our results demonstrate that EGF reduces both the basal number of 1,25(OH)2D3 binding sites and the heterologous up-regulation of the 1,25(OH)2D3 receptor. The current data suggest that EGF reduces heterologous up-regulation of the 1,25(OH)2D3 receptor independent of as well as dependent on the cAMP messenger system. The EGF effect is nor primarily located at the PTH receptor, at cAMP phosphodiesterase, or at protein kinase A level.
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PMID:Modulation by epidermal growth factor of the basal 1,25(OH)2D3 receptor level and the heterologous up-regulation of the 1,25(OH)2D3 receptor in clonal osteoblast-like cells. 165 78


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