Protein prenylcysteine analog inhibits agonist-receptor-mediated signal transduction in human platelets

Huzoor-Akbar, Wenjing Wang, Robyn Kornhauser, Craig Volker, Jeffry B. Stock

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Signal transduction components, including the Ras superfamily of low molecular weight GTP-binding proteins and the γ subunits of heterotrimeric G proteins, are reversibly carboxyl methylated at C-terminal prenylcysteine residues. We have previously shown that the prenylcysteine analog N-acetyl-S-trans,trans-farnesyl-L-cysteine (AFC) inhibits carboxyl methylation of these proteins in human platelets. Here we show that concentrations of AFC that inhibit Ras carboxyl methylation (10-50 μM) also block responses to agonists such as ADP, collagen, arachidonic acid, U46619 (a stable analog of prostaglandin H2), thrombin, and guanosine 5′-[γ-thio]triphosphate. AFC does not inhibit aggregation induced by effectors such as ionomycin, phorbol 12,13-dibutyrate, and bacterial phospholipase C that bypass G proteins to activate platelets at the level of cytosolic Ca2+ concentration and protein kinase C. These findings indicate that AFC inhibits agonist-receptor-mediated signal transduction in human platelets.

Original languageEnglish (US)
Pages (from-to)868-872
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - Feb 1 1993

All Science Journal Classification (ASJC) codes

  • General


  • Carboxyl methylation
  • GTP-binding proteins
  • Prenylated proteins


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