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)

The physiologic role of cyclic adenosine monophosphate (cAMP) in the growth control of a spectrum of human cancer lines, including leukemic lines, and v-rasH oncogene-transformed NIH/3T3 cells is demonstrated by the use of site-selective cAMP analogs. These cAMP analogs, which can select either of the two known cAMP binding sites of the cAMP receptor protein, induce potent growth inhibition, phenotypic change, and differentiation (leukemic cells) of cancer cells at micromolar concentrations with no sign of cytotoxicity. The growth inhibition parallels selective modulation of cAMP-dependent protein kinase isozymes, type I versus type II, and suppression of cellular proto-oncogene expression. Site-selective cAMP analogs thus provide new biological tools for investigating cell proliferation and differentiation and also for the improved management of human cancers.
...
PMID:Site-selective cyclic AMP analogs as new biological tools in growth control, differentiation, and proto-oncogene regulation. 255 68

The Xenopus c-mos proto-oncogene product, pp39mos, accumulates in the unfertilized egg during maturation, is hyperphosphorylated and exhibits protein kinase activity. On fertilization, or soon after the completion of meiosis, the accumulated pp39mos undergoes selective proteolysis. Using an in vitro protease assay system, we show here that this specific proteolysis is caused by the calcium-dependent cysteine protease, calpain.
...
PMID:Specific proteolysis of the c-mos proto-oncogene product by calpain on fertilization of Xenopus eggs. 253 Dec 91

The c-fms proto-oncogene is a member of a gene family that has been implicated in tumorigenesis. Glycoproteins encoded by c-fms were identified in cat spleen cells by means of an immune-complex kinase assay performed with monoclonal antibodies to v-fms-coded epitopes. The major form of the normal cellular glycoprotein has an apparent molecular weight of 170,000 and, like the product of the viral oncogene, serves as a substrate for an associated tyrosine-specific protein kinase activity in vitro. The results suggest that the transforming glycoprotein specified by v-fms is a truncated form of a c-fms-coded growth factor receptor.
...
PMID:The product of the c-fms proto-oncogene: a glycoprotein with associated tyrosine kinase activity. 258 Mar 48

The Xenopus laevis genome was probed by Southern Blot analysis for the presence of sequences homologous to mammalian or avian proto-oncogenes. Hybridization conditions were strictly defined with a known proto-oncogene to detect a positive signal with DNA sequences having at least 60 to 64% homology. In such conditions thirteen genes representing different oncogene families exhibited positive hybridizations with specific DNA restriction fragments. Members of the protein kinase oncogene family were detected including abl, erbB, fes, fms, ros, raf and mos. Ets, rel, and the steroid hormone related receptor erbA also gave positive signals with specific Xenopus DNA fragments. Proto-oncogenes raf and the ras family, N-ras, H-ras and c-ral, gave the strongest hybridizations and the signals remained positive in high stringency wash conditions. This study confirms the relative conservation of these genes during evolution and opens the possibility of studying their role in one of the best characterized systems of embryonic development.
...
PMID:Detection of proto-oncogenes in the genome of the amphibian Xenopus laevis. 265 8

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

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.
...
PMID:Evidence for the involvement of the proto-oncogene c-mos in mammalian meiotic maturation and possibly very early embryogenesis. 284 Feb 83

In studies of regulation of the growth and differentiated function of the thyroid follicular cell, we have employed the FRTL5 cell line to evaluate both the effects of agents that activate protein kinase-C (PKC) and their interaction with other agents that influence the growth and/or function of the FRTL5 cell. The PKC activator tetradecanoyl-phorbol acetate (TPA) alone induced a time- and concentration-dependent stimulation of the incorporation of [3H]thymidine into the DNA of quiescent FRTL5 cells, an effect anteceded by an increase in the levels of the mRNAs of the proto-oncogene c-myc and associated with a stimulation of cell replication. TPA also produced a dose-dependent inhibition of the low levels of radioiodine uptake in quiescent FRTL5 cells. These effects of TPA were unaccompanied by any change in the cellular cAMP concentration. TPA also modified a variety of responses to TSH, attenuating the TSH-induced stimulation of [3H]thymidine incorporation into DNA, cell replication, cAMP generation, and iodine uptake. Inhibition of TSH-stimulated growth and iodine uptake by TPA could not be ascribed solely to a decrease in cAMP generation, since TPA also inhibited the increase in [3H]thymidine incorporation and iodide uptake induced by the cAMP analog (Bu)2cAMP. In contrast, the independent stimulatory effects of TPA and insulin-like growth factor I (IGF-I) on [3H]thymidine incorporation and cell replication were at least additive when the two stimulators were added together. We have previously reported that both TSH and (Bu)2cAMP amplify the enhancement of DNA synthesis and cell replication in FRTL5 cells induced by IGF-I, and that the response of DNA synthesis to IGF-I is also enhanced if cells are preincubated with either TSH or (Bu)2cAMP. Both the former amplification of mitogenesis and the latter priming effect were decreased by exposing cells to TPA concomitant with their exposure to TSH or (Bu)2cAMP. The effects of TPA were mimicked by other activators of PKC, but not by a phorbol ester that fails to activate this enzyme. In general, we conclude that in the FRTL5 cell, regulation of cell growth is extremely complex; there are at least three mitogenic pathways that are separate from but interact with one another. The first is the well known cAMP-dependent pathway, which is activated by TSH. The second is activated by IGF-I and is cAMP independent. These two pathways interact to produce a marked amplification of their individual mitogenic effects. The third pathway is that stimulated by TPA and involves activation of PKC.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Independent and interactive effects of tetradecanoyl phorbol acetate on growth and differentiated functions of FRTL5 cells. 284 Oct 99

The c-fms proto-oncogene product is a transmembrane glycoprotein that is probably identical to the cell surface receptor for the mononuclear phagocyte colony stimulating factor, CSF-1. An analogous glycoprotein encoded by the viral oncogene v-fms includes the extracellular ligand-binding domain, membrane spanning segment, and cytoplasmic tyrosine kinase domain of the CSF-1 receptor. The v-fms and c-fms gene products differ significantly at their distal carboxylterminal ends where the truncated viral transforming protein has lost a single tyrosine residue (tyr969) that may negatively regulate the receptor kinase activity. Introduction of v-fms into a CSF-1 dependent murine macrophage cell line induced factor independence and tumorigenicity by a nonautocrine mechanism. Thus, although the v-fms gene product can bind CSF-1, its constitutive tyrosine-specific protein kinase provides growth stimulatory signals in the absence of ligand. Transfection of human c-fms cDNA into mouse NIH-3T3 cells conferred a CSF-1 responsive phenotype. Although neither the wild-type c-fms (tyr969) gene nor a mutant c-fms (phe969) allele induced transformation of NIH-3T3 cells, cotransfection with human CSF-1 cDNA gave rise to transformed foci. In cells cotransfected with the CSF-1 gene, the efficiency of focus formation induced by the mutant c-fms (phe969) gene was greater than that of the wild-type gene and equivalent to that of v-fms alone. A chimeric v-fms/c-fms molecule in which the carboxylterminus of the v-fms gene product was replaced by the corresponding region of the wild type c-fms (tyr969) was weakly transforming, whereas chimeric molecules containing phe969 transformed NIH-3T3 cells efficiently. Thus, complete oncogenic activation of the c-fms gene appears to require two events: one which alters a putative negative regulatory site of tyrosine phosphorylation, and a second which phenocopies a ligand-induced conformational change.
...
PMID:Requirements for transformation by the fms oncogene product (CSF-1 receptor). 284 95

Transcription of proto-oncogene fos is induced by elevated levels of intracellular cAMP. We report that human c-fos promoter recombinants transfected into rat pheochromocytoma cells (PC12) and human choriocarcinoma cells (JEG-3) are induced by stimulation of adenylate cyclase and that this induction is diminished considerably in the mutant PC12 cell line A126-1B2, which is deficient in cAMP-dependent protein kinase II. An element centered at position -60 of the c-fos promoter, which encompasses a consensus cAMP response element (CRE), is sufficient to confer cAMP responsiveness to a herpes thymidine kinase/CAT fusion gene. The specific binding of a nuclear protein to the c-fos CRE can be competed by the somatostatin and alpha-chorionic gonadotropin (alpha-CG) promoter regions that contain CREs. Gel mobility shift assays with double-stranded oligonucleotides containing either the wild-type or mutated c-fos CRE sequence have demonstrated that binding occurs only to the wild-type CRE. The nuclear factor binding to the c-fos CRE is likely to be transcription factor CREB (CRE nuclear binding protein), because an affinity-purified 43-kD CREB isolated from PC12 cells binds efficiently in a DNA footprinting assay. Thus, regulation of the c-fos gene transcription appears to involve a mechanism common to many genes that respond to cAMP as a second message leading to cell growth and differentiation.
...
PMID:Induction of proto-oncogene fos transcription through the adenylate cyclase pathway: characterization of a cAMP-responsive element. 285 Sep 67

The macrophage colony-stimulating factor, CSF-1 (M-CSF), is a homodimeric glycoprotein required for the lineage-specific growth of cells of the mononuclear phagocyte series. Apart from its role in stimulating the proliferation of bone marrow-derived precursors of monocytes and macrophages, CSF-1 acts as a survival factor and primes mature macrophages to carry out differentiated functions. Each of the actions of CSF-1 are mediated through its binding to a single class of high-affinity receptors expressed on monocytes, macrophages, and their committed progenitors. The CSF-1 receptor (CSF-1R) is encoded by the c-fms proto-oncogene, and is one of a family of growth factor receptors that exhibits an intrinsic tyrosine-specific protein kinase activity. Transduction of c-fms sequences as a viral oncogene (v-fms) in the McDonough (SM) and HZ-5 strains of feline sarcoma virus has resulted in alterations in receptor coding sequences that affect its activity as a tyrosine kinase and provide persistent signals for cell growth in the absence of its ligand. The genetic alterations in the c-fms gene that unmask its latent transforming potential abrogate its lineage-specific activity and enable v-fms to transform a variety of cells that do not normally express CSF-1 receptors.
...
PMID:Colony-stimulating factor-1 receptor (c-fms). 285 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---