Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guanosine 5'-O-(thiotriphosphate) (GTP gamma S), an activator of guanine nucleotide binding protein (G protein), increased prostaglandin E2 (PGE2) production in saponin permeabilized rat thymic epithelial cells, TEA3A1. Aluminum fluoride (A1F4-), a cell permeable G protein activator, also stimulated PGE2 production and arachidonic acid (AA) release from TEA3A1 cells. Using A1F4- instead of GTP gamma S as a G-protein activator, we have investigated the mechanism of G-protein mediated stimulation of PGE2 production in TEA3A1 cells. Results from our experiments indicate that G protein mediated activation of AA metabolism in TEA3A1 cells is regulated by two independent mechanisms. One is by the stimulation of AA release via the activation of PLA2 enzymatic activity through PLC and PKC mediated pathway and the other is by a concomitant inhibition of AA incorporation into membrane phospholipids.
Biochem Mol Biol Int 1993 Nov
PMID:Guanine nucleotide-binding protein stimulates arachidonic acid metabolism in TEA3A1 thymic epithelial cells by stimulating release and inhibiting incorporation of arachidonic acid. 829 92

A differentiated liver cell (HepG2), which exhibits a dose-dependent growth-stimulatory and growth-inhibitory response to heparin-binding fibroblast growth factor type 1 (FGF-1), displays high- and low-affinity receptor phenotypes and expresses specific combinatorial splice variants alpha 1, beta 1, and alpha 2 of the FGF receptor (FGF-R) gene (flg). The extracellular domains of the alpha and beta variants consist of three and two immunoglobulin loops, respectively, while the intracellular variants consist of a tyrosine kinase (type 1) isoform and a kinase-defective (type 2) isoform. The type 2 isoform is also devoid of the two major intracellular tyrosine autophosphorylation sites (Tyr-653 and Tyr-766) in the type 1 kinase. An analysis of ligand affinity, dimerization, autophosphorylation, and interaction with src homology region 2 (SH2) substrates of the recombinant alpha 1, beta 1, and alpha 2 isoforms was carried out to determine whether dimerization of the combinatorial splice variants might explain the dose-dependent opposite mitogenic effects of FGF. Scatchard analysis indicated that the alpha and beta isoforms exhibit low and high affinity for ligand, respectively. The three combinatorial splice variants dimerized in all combinations. FGF enhanced dimerization and kinase activity, as assessed by receptor autophosphorylation. Phosphopeptide analysis revealed that phosphorylation of Tyr-653 was reduced relative to phosphorylation of Tyr-766 in the type 1 kinase component of heterodimers of the type 1 and type 2 isoforms. The SH2 domain substrate, phospholipase C gamma 1 (PLC gamma 1), associated with the phosphorylated type 1-type 2 heterodimers but was phosphorylated only in preparations containing the type 1 kinase homodimer. The results suggest that phosphorylation of Tyr-653 within the kinase catalytic domain, but not Tyr-766 in the COOH-terminal domain, may be stringently dependent on a trans intermolecular mechanism within FGF-R kinase homodimers. Although phosphotyrosine 766 is sufficient for interaction of PLC gamma 1 and other SH2 substrates with the FGF-R kinase, phosphorylation and presumably activation of substrates require the kinase homodimer and phosphorylation of Tyr-653. We propose that complexes of phosphotyrosine 766 kinase monomers and SH2 domain signal transducers may constitute unactivated presignal complexes whose active or inactive fate depends on homodimerization with a kinase or heterodimerization with a kinase-defective monomer, respectively. The results suggest a mechanism for control of signal transduction by different concentrations of ligand through heterodimerization of combinatorial splice variants from the same receptor gene.
Mol Cell Biol 1993 Jul
PMID:Control of fibroblast growth factor receptor kinase signal transduction by heterodimerization of combinatorial splice variants. 832 Nov 98

Erwinia atroseptica 36A cells were transformed by the recombinant plasmid pPL5-1 (a derivative of the vector plasmid pUC19) containing pelb and pelc genes which encode pectate lyases of Erwinia chrysanthemi ENA49. Synthesis of pectate lyases PLB and PLC determined by the cloned pel genes is constitutive in Erwinia atroseptica 36ApPL5-1 cells and not inducible by sodium polypectate. The major part of these enzymes was accumulated in the periplasmic fraction of Erwinia atroseptica and cells were unable to efficiently secrete the enzymes into the cultural medium. Synthesis and secretion of the native pectate lyases by Erwinia atroseptica harboring the plasmid were as efficient as by the parental cells. The obtained results suggest the high specificity of pectate lyase secretory systems of kindred Erwinias.
Mol Gen Mikrobiol Virusol
PMID:[Expression of pel genes of Erwinia chrysanthemi ENA49 in Erwinia carotovora var. atroseptica 36A cells]. 837 22

A five min. incubation of peripheral blood mononuclear cells (PBMN) with either phytohaemagglutinin (PHA) or concanavalin A (ConA) resulted in distinct subcellular redistribution patterns of phosphatidylinositol 4,5-bisphosphate phospholipase C [PtdIns(4,5)P2-PLC] and myo-inositol 1,4,5-trisphosphate monophosphatase [Ins(1,4,5)P3-monophosphatase] activities. When compared to control cells, PHA-treated PBMN cells displayed a significant increase of PtdIns(4,5)P2-PLC and Ins(1,4,5)P3-monophosphatase relative specific activities in the nuclear fraction along with an increment (D) in enzyme amount of 6.5% and 7.3%, respectively. Incubation with B66.6, an anti-CD4 monoclonal antibody (Mab) which specifically activates CD4(+)-T cells in the absence of any other stimuli, also induced changes of these activities in the nuclear fraction, thus mimicking the effect of PHA observed in helper T cell subpopulation. No changes were detected after incubation of PBMN cells with the non mitogenic anti-CD4 MAb 101-69, or with an anti-CD3 MAb which activates T cells only in the presence of a second stimulus. On the other hand, after incubation with ConA, PtdIns(4,5)P2-PLC relative specific activity was enhanced in the microsomal fraction while the Ins(1,4,5)P3-monophosphatase activity increased in both nuclear and microsomal fractions and decreased in cytosol. An increment D of 4.6% and 10.9% for PtdIns(4,5)P2-PLC and Ins(1,4,5)P3-monophosphatase, respectively, was measured in the microsomal fraction. Only after three days of incubation with a mitogenic anti-CD2 MAb Lau-2.1.2, the PtdIns(4,5)P2-PLC activity increased in the particulate fraction of PBMN similar to ConA treatment.
Cell Mol Biol (Noisy-le-grand) 1993 Feb
PMID:Lectins and anti-T monoclonal antibodies-induced changes of second messengers generating enzymes in human peripheral blood mononuclear cells. 838 19

The plcA gene of Listeria monocytogenes encodes a secreted phosphatidylinositol-specific phospholipase C (Pl-PLC). Recent studies have established that transposon mutations within plcA result in avirulence for mice and pleiotropic effects when examined in tissue-culture models of infection. Genetic analysis reveals that many of the effects of the transposon insertions are due to loss of readthrough transcription from plcA into the downstream gene prfA, which encodes an essential transcription factor of numerous L. monocytogenes virulence genes. Construction of an in-frame deletion within plcA had no effect on expression of prfA thus allowing direct assignment of a role of the Pl-PLC in pathogenesis. Pl-PLC was shown to play a significant role in mediating escape of L. monocytogenes from phagosomes of primary murine macrophages. Interestingly, this defect manifested itself in vivo in the liver but not in the spleen of infected mice.
Mol Microbiol 1993 Apr
PMID:Dual roles of plcA in Listeria monocytogenes pathogenesis. 838 29

A series of pieces of evidence have shown that Ras protein acts as a transducer of the platelet-derived growth factor (PDGF) receptor-mediated signaling pathway: (i) formation of Ras.GTP is detected immediately on PDGF stimulation, and (ii) a dominant inhibitory mutant Ras, as well as a neutralizing anti-Ras antibody, can interfere with PDGF-induced responses. On the other hand, several signal transducing molecules including phosphatidylinositol 3-kinase (PI3-K), GTPase-activating protein (GAP), and phospholipase C gamma (PLC gamma) bind directly to the PDGF receptor and become tyrosine phosphorylated. Recently, it was shown that specific phosphorylated tyrosines of the PDGF receptor are responsible for interaction between the receptor and each signaling molecule. However, the roles of these signaling molecules have not been elucidated, and it remains unclear which molecules are implicated in the Ras pathway. In this study, we measured Ras activation in cell lines expressing mutant PDGF receptors that are deficient in coupling with specific molecules. In fibroblast CHO cells, a mutant receptor (Y708F/Y719F [PI3-K-binding sites]) was unable to stimulate Ras, whereas another mutant (Y739F [the GAP-binding site]) could do so, suggesting an indispensable role of PI3-K or a protein that binds to the same sites as PI3-K for PDGF-stimulated Ras activation. By contrast, both of the above mutants were capable of stimulating Ras protein in a pro-B-cell line, BaF3. Furthermore, a mutant receptor (Y977F/Y989F [PLC gamma-binding sites]) could fully activate Ras, and the direct activation of protein kinase C and calcium mobilization had almost no effect on the GDP/GTP state of Ras in this cell line. These results suggest that, in the pro-B-cell transfectants, each of the above pathways (PI3-K, GAP, and PLC gamma) can be eliminated without a loss of Ras activation. It remains unclear whether another unknown essential pathway which regulates Ras protein exists within BaF3 cells. Therefore, it is likely that several different PDGF receptor-mediated signaling pathways function upstream of Ras, and the extent of the contribution of each pathway for the regulation of Ras may differ among different cell types.
Mol Cell Biol 1993 Jun
PMID:Platelet-derived growth factor receptor mediates activation of ras through different signaling pathways in different cell types. 838 43

We identified a putative Saccharomyces cerevisiae homolog of a phosphoinositide-specific phospholipase C (PI-PLC) gene, PLC1, which encodes a protein most similar to the delta class of PI-PLC enzymes. The PLC1 gene was isolated during a study of yeast strains that exhibit defects in chromosome segregation. plc1-1 cells showed a 10-fold increase in aberrant chromosome segregation compared with the wild type. Molecular analysis revealed that PLC1 encodes a predicted protein of 101 kDa with approximately 50 and 26% identity to the highly conserved X and Y domains of PI-PLC isozymes from humans, bovines, rats, and Drosophila melanogaster. The putative yeast protein also contains a consensus EF-hand domain that is predicted to bind calcium. Interestingly, the temperature-sensitive and chromosome missegregation phenotypes exhibited by plc1-1 cells were partially suppressed by exogenous calcium.
Mol Cell Biol 1993 Jul
PMID:A mutation in PLC1, a candidate phosphoinositide-specific phospholipase C gene from Saccharomyces cerevisiae, causes aberrant mitotic chromosome segregation. 839 35

Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphatidylinositol-specific phospholipase C (PI-PLC) generates two second messengers, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. The polymerase chain reaction was used to isolate a Saccharomyces cerevisiae gene (PLC1) that encodes a protein of 869 amino acids (designated Plc1p) that bears greatest resemblance to the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain arrangement. Plc1p contains the conserved X and Y domains found in all higher eukaryotic PI-PLCs (51 and 29% identity, respectively, to the corresponding domains of rat delta 1 PI-PLC) and also contains a presumptive Ca(2+)-binding site (an E-F hand motif). Plc1p, modified by in-frame insertion of a His6 tract and a c-myc epitope near its amino terminus, was overexpressed from the GAL1 promoter, partially purified by nickel chelate affinity chromatography, and shown to be an active PLC enzyme in vitro with properties similar to those of its mammalian counterparts. Plc1p activity was strictly Ca2+ dependent: at a high Ca2+ concentration (0.1 mM), the enzyme hydrolyzed PIP2 at a faster rate than phosphatidylinositol, and at a low Ca2+ concentration (0.5 microM), it hydrolyzed PIP2 exclusively. Cells carrying either of two different deletion-insertion mutations (plc1 delta 1::HIS3 and plc1 delta 2::LEU2) were viable but displayed several distinctive phenotypes, including temperature-sensitive growth (inviable above 35 degrees C), osmotic sensitivity, and defects in the utilization of galactose, raffinose, and glycerol at permissive temperatures (23 to 30 degrees C). The findings reported here suggest that hydrolysis of PIP2 in S. cerevisiae is required for a number of nutritional and stress-related responses.
Mol Cell Biol 1993 Sep
PMID:Genetic and biochemical characterization of a phosphatidylinositol-specific phospholipase C in Saccharomyces cerevisiae. 839 15

Engagement of the B-cell antigen receptor complex induces immediate activation of receptor-associated Src family tyrosine kinases including p55blk, p59fyn, p53/56lyn, and perhaps p56lck, and this response is accompanied by tyrosine phosphorylation of distinct cellular substrates. These kinases act directly or indirectly to phosphorylate and/or activate effector proteins including p42 (microtubule-associated protein kinase) (MAPK), phospholipases C-gamma 1 (PLC gamma 1) and C-gamma 2 (PLC gamma 2), phosphatidylinositol 3-kinase (PI 3-K), and p21ras-GTPase-activating protein (GAP). Although coimmunoprecipitation results indicate that the Src family protein tyrosine kinases interact physically with some of these effector molecules, the molecular basis of this interaction has not been established. Here, we show that three distinct sites mediate the interaction of these kinases with effectors. The amino-terminal 27 residues of the unique domain of p56lyn mediate association with PLC gamma 2, MAPK, and GAP. Binding to PI 3-K is mediated through the Src homology 3 (SH3) domains of the Src family kinases. Relatively small proportions of cellular PI 3-K, PLC gamma 2, MAPK, and GAP, presumably those which are tyrosine phosphorylated, bind to the SH2 domains of these kinases. Comparative analysis of binding activities of Blk, Lyn, and Fyn shows that these kinases differ in their abilities to associate with MAPK and PI 3-K, suggesting that they may preferentially bind and subsequently phosphorylate distinct sets of downstream effector molecules in vivo. Fast protein liquid chromatography Mono Q column-fractionated MAPK maintains the ability to bind bacterially expressed Lyn, suggesting that the two kinases may interact directly.
Mol Cell Biol 1993 Sep
PMID:Mapping of sites on the Src family protein tyrosine kinases p55blk, p59fyn, and p56lyn which interact with the effector molecules phospholipase C-gamma 2, microtubule-associated protein kinase, GTPase-activating protein, and phosphatidylinositol 3-kinase. 839 16

Schwartz-Jampel syndrome (SJS, MIM 255800), also known as chondrodystrophic myotonia, is a rare autosomal recessive disorder characterized by generalized myotonia, skeletal abnormalities and facial dysmorphism. Using homozygosity mapping, we localized the SJS locus to chromosome 1p34-p36.1 in a 8 cM interval flanked by markers D1S199 and D1S234. Families of different ethnic backgrounds (Tunisia and South Africa) showed genetic linkage to the same locus. Moreover, one Algerian family also demonstrated evidence of genetic linkage to 1p34-p36.1. Taken altogether, our results suggest genetic homogeneity, at least in the group of families analyzed.
Hum Mol Genet 1995 Sep
PMID:Localization of the Schwartz-Jampel syndrome (SJS) locus to chromosome 1p34-p36.1 by homozygosity mapping. 854 52


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