PDGF induction of tyrosine phosphorylation of GTPase activating protein

Molloy, Christopher J.; Bottaro, Donald P.; Fleming, Timothy P.; Marshall, Mark S.; Gibbs, Jackson B.; Aaronson, Stuart A.

doi:10.1038/342711a0

Cited by 461 publications

(179 citation statements)

References 27 publications

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“…Tyrosine phosphorylation of mammalian GAP has long been known (Ellis, Moran, McCormick, & Pawson, 1990;Molloy et al, 1989;Park & Jove, 1993) and more intriguingly p190rho-GAP has been shown to be a substrate of mammalian low molecular weight PTPase . Furthermore it has been reported that phosphorylation of mammalian GAP by the src tyrosine kinase reduces GAP activity (Giglione, Gonfloni, & Parmeggiani, 2001).…”

Section: Discussionmentioning

confidence: 99%

In Saccharomyces cerevisiae an unbalanced level of tyrosine phosphorylation down-regulates the Ras/PKA pathway

Magherini

Busti

Gamberi

et al. 2006

The International Journal of Biochemistry & Cell Biology

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The role of tyrosyl phosphorylation/dephosphorylation in the budding yeast Saccharomyces cerevisiae, whose genome does not encode typical tyrosyne kinases, has long remained elusive. Nevertheless, several protein kinases phosphorylating poly(TyrGlu) substrates have been identified. In this work, we use the expression of the low molecular weight tyrosine phosphatase Stp1 from the distantly related yeast Schizosaccharomyces pombe, as a tool to investigate whether an unbalanced level of protein tyrosine phosphorylation affects S. cerevisiae growth and metabolism. We correlate the previously reported down-regulation of the phosphotyrosine level brought about by overexpression of Stp1 with a large number of phenotypes indicative of down-regulation of the Ras pathway. These phenotypes include reduction in both glucose-and acidification-induced GTP loading of the Ras2 protein and cAMP signaling, impaired growth on a non-fermentable carbon source, alteration of cell cycle parameters, delayed recovery from nitrogen starvation, increased heat-shock resistance, attenuated pseudohyphal and invasive growth. Genetic data suggest that Stp1 acts either at, or above, the level of Ras2, possibly on the Ira proteins. Consistently, Stp1 was found to bind to immunoprecipitated Ira2. Since a catalytically inactive mutant form of Stp1 (Stp1 C11S ) effectively binds to Ira2 without producing any effect on yeast physiology, we conclude that down-regulation of the Ras pathway by Stp1 requires its phosphatase activity. In conclusion, our data suggest a possible cross-talk between tyrosine phosphorylation and the Ras pathway in yeast.

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Section: Discussionmentioning

confidence: 99%

In Saccharomyces cerevisiae an unbalanced level of tyrosine phosphorylation down-regulates the Ras/PKA pathway

Magherini

Busti

Gamberi

et al. 2006

The International Journal of Biochemistry & Cell Biology

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“…It is well established that FGFR-1 activation leads to phosphorylation of Shc and activation of Raf-1 and MAPK (Klint et al, 1995;Shaoul et al, 1995;Wang et al, 1994) whereas other signal transduction molecules which have been implicated in chemotactic signaling i.e. PI 3-kinase and rasGAP do not bind to or become activated by FGFR-1 (Molloy et al, 1989;WennstroÈ m et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor receptor-1 mediates chemotaxis independently of direct SH2-domain protein binding

et al. 1998

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Endothelial cells expressing ®broblast growth factor receptor-1 (FGFR-1) migrate and proliferate in response to treatment with FGF. We analysed ligand-induced migration and proliferation of porcine aortic endothelial cells expressing wild-type FGFR-1, point-mutated Y766F FGFR-1, unable to activate phospholipase C-g1 (PLCg1), or carboxyl-terminally truncated FGFR-1, lacking either 48 (from amino acid 774 in the FGFR-1 sequence) or 63 (from amino acid 759) amino acid residues of the C-terminal tail. The truncated CT63 FGFR-1 mutant failed to mediate chemotaxis, but was in response to ligand stimulation capable of mediating proliferation of the cells, stimulation of MAP kinase activity and tyrosine phosphorylation of FRS2, an FGFR-1 speci®c signaling molecule. The defect in migration-capacity of CT63 was not due to loss of Y766, and thereby PLC-g1 activation, since cells expressing the mutant Y766F FGFR-1 migrated as e ciently as the wild-type receptor cells. Induction of phospholipase A 2 (PLA 2 ) activity by the activated FGFR-1 was dependent on the presence of Y766, and was therefore also not critical for the chemotactic response. Although the FGFR-1 only very ine ciently mediates activation of phosphatidylinositol 3' kinase (PI 3-kinase), the PI 3-kinase inhibitor wortmannin suppressed wild-type FGFR-1 mediated migration. We conclude that the signal transduction pathway for FGFR-1 mediated migration is independent of phosphotyrosine residues in the receptor and requires activation of a wortmannin-sensitive enzyme.

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“…p125 GAP is a cytosolic polypeptide that catalyzes the GTPase activity of p21 ras [6,7]. In growth ft~ctor-stimulated and tyrosine kinase-transformed rat fibrobasts, p125 GAP becomes tyrosine phosphorylated and is t~anslocated from the cytosol to cell membranes, where it interacts with its biological target, p21 ras, as well as with actiwlted growth factor receptors [8][9][10][11][12][13][14][15][16][17][18]. It has been reported that p21 ras is responsible for the activation of mitogen-activated protein (MAP) kinases cascade [19], and that MAP kinases are fiwolved in the mechanisms of activation of NADPH oxidase [20][21][22], the enzymatic system responsible for the generation of reactive oxygen metabolites [23][24][25][26][27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Tyrosine phosphorylation and subcellular redistribution of p125 ras guanosine triphosphatase‐activating protein in human neutrophils stimulated with FMLP

et al. 1996

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In this paper, we show that the p125 ras guanosine triphosphatase-activating protein (p125 GAP) is present in the cytosol of human neutrophils and is transiently tyrosine phosphorylated and transiocated to the membranes upon cell activation with formyl-methionyl-leucyl-phenylalanine (FMLP). When concanavalin A (ConA) or phorbol 12-myristate 13-acetate (PMA), which both induced a long-lasting respiratory burst, were used as stimuli, tyrosine phosphorylation and translocation of p125 GAP did not occur.

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PDGF induction of tyrosine phosphorylation of GTPase activating protein

Cited by 461 publications

References 27 publications

In Saccharomyces cerevisiae an unbalanced level of tyrosine phosphorylation down-regulates the Ras/PKA pathway

In Saccharomyces cerevisiae an unbalanced level of tyrosine phosphorylation down-regulates the Ras/PKA pathway

Fibroblast growth factor receptor-1 mediates chemotaxis independently of direct SH2-domain protein binding

Tyrosine phosphorylation and subcellular redistribution of p125 ras guanosine triphosphatase‐activating protein in human neutrophils stimulated with FMLP

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