Ca2+ channel activation by pdgf-induced tyrosine phosphorylation and ras gtp-binding proteins in rat glomerular mesangial cells

B. N. Ling, H. Ma, H. Matsunaga, B. Schieffer, M. B. Marrero

Research output: Contribution to journalArticle

Abstract

We investigated the signaling pathways mediating 1 pS Ca2+ channel activation by platelet-derived growth factor (PDGF) in cultured rat mesangial cells. In cellattached patches, intrapipette PDGF-BB (50 ng/ml) dramatically stimulates channel activity (P < 0.003; n = 6). Tyrosine kinase inhibition (100 (M genistein or 10 /M tryphostin 9) abolished PDGF-induced channel activation (P < 0.02; n = 6). In excised patches, the effect of tyrosine kinase inhibition could be reversed by cytoplasmic exposure to 200 /M GTPyS (P < 0.02; n = 4). In contrast, 200 ftM GDPβS inhibited PDGF-induced channel activity (P < 0.04; n = 6). Pretreatment with pertussis toxin (250 ng/ml PTX) had no effect on PDGF-induced channel activity (P = 0.45; n = 6). When excised patches were exposed to anti-Aos antibody (5 /ig/ml), PDGF-induced channel activity was abolished (P < 0.002; n = 11). Western immunoblots revealed that PDGF-BB binding also stimulates the formation of a membrane-bound complex consisting of growth factor receptor-binding protein 2 (GRB-2), son of sevenless (SOS), and the PDGF βreceptor itself. Complex formation was abolished by genistein. In mesangial cells, the intrinsic tyrosine kinase activity of the PDGF βreceptor stimulates the formation of a membrane-bound GRB-2/SOS/PDGF βreceptor complex, and activation of the PTX-insensitive GTP-binding protein, p2l-Ras, which finally leads to the opening of 1 pS Ca2 channels.

Original languageEnglish (US)
Pages (from-to)240a
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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