cAMP does not inhibit convulxin-induced tyrosyl-phosphorylation of human platelet proteins, including PLCγ2, but completely blocks the integrin α(IIb)β3- dependent dephosphorylation step: Comparisons with RGDS peptide, cytochalasin D, and phenylarsine oxide

Ivo M.B. Francischetti, Célia R. Carlini, Jorge A. Guimarães

Research output: Contribution to journalArticlepeer-review

Abstract

Convulxin (Cvx) isolated from Crotalus durissus terrificus venom, induces platelet aggregation, phospholipase C (PLC) activation, and tyrosyl- phosphorylation (PTP) of multiple proteins, including PLCγ2 by a mechanism independent of integrin {IIb)β3. However, PTP induced by Cvx is followed by a dephosphorylation step in a platelet aggregation-dependent manner. Here we show that increasing intraplatelet content of cAMP with forskolin is associated with the inhibition of Cvx-induced platelet aggregation, ATP secretion, and inositol-phosphates production. However, the early onset of Cvx-induced PTP is not sensitive to cAMP (including PLCγ2), and it also occurs in the presence of integrin α(IIb)β3-antagonist (RGDS peptide, RGDS) or inhibitors of actin polymerization (cytochalasin D, CD) and tyrosine-phosphatases (phenylarsine oxide, PAO). However, forskolin, RGDS, and CD prevented the dephosphorylation step together with inhibition of platelet aggregation, whereas in the presence of phenylarsine oxide (PAO) the dephosphorylation step was replaced by an increase in the number and intensity of tyrosyl-phosphorylated proteins. Our data provide evidence to conclude that (i) cAMP inhibits platelet aggregation at a downstream site to PLCγ2 tyrosyl-phosphorylation; (ii) Cvx-induced PTP is independent on integrin α(IIb)β3 engagement, actin polymerization, and tyrosine- phosphatases activation; (iii) integrin α(IIb)β3 mediates the dephosphorylation step in a platelet aggregation-dependent manner; and (iv) Cvx and collagen stimulate platelets by a similar signal transduction pathway.

Original languageEnglish (US)
Pages (from-to)255-262
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume354
Issue number2
DOIs
StatePublished - Jun 15 1998
Externally publishedYes

Keywords

  • Collagen
  • Convulxin
  • GPVI
  • PLCγ2
  • Snake venoms
  • Tyrosine- kinases
  • Tyrosine-phosphatases
  • cAMP

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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