Anti-CD9 monoclonal antibody elicits staurosporine inhibitable phosphatidylinositol 4,5-bisphosphate hydrolysis, phosphatidylinositol 3,4-bisphosphate synthesis, and protein-tyrosine phosphorylation in human platelets

FEBS Lett. 1993 May 17;322(3):285-90. doi: 10.1016/0014-5793(93)81587-p.

Abstract

Phosphoinositide metabolism elicited by anti-CD9 monoclonal antibody, a well-characterized platelet activator, was studied using acetylsalicylic acid-treated human platelets. TP82, which is an anti-CD9 monoclonal antibody, induced classical phosphatidylinositol 4,5-bisphosphate hydrolysis, as monitored by intracellular Ca2+ mobilization and phosphatidic acid production, and synthesis of phosphatidylinositol 3,4-bisphosphate, which is a major component of newly-described 3-phosphorylated inositol phospholipids produced during platelet activation. These changes were severely inhibited by 1 microM staurosporine, a potent, though non-selective, protein kinase inhibitor, which also abolished TP82 induction of tyrosine phosphorylation of multiple platelet proteins. Protein-tyrosine phosphorylation appears necessary to initiate both the classical phosphoinositide turnover and synthesis of the newly-described 3-phosphorylated inositol phospholipids in anti-CD9 monoclonal antibody-induced platelet activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Antibodies, Monoclonal / pharmacology*
  • Antigens, CD / immunology*
  • Blood Platelets / metabolism*
  • Humans
  • Membrane Glycoproteins / immunology
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates*
  • Phosphatidylinositols / biosynthesis*
  • Phosphatidylinositols / metabolism*
  • Protein Kinase C / antagonists & inhibitors*
  • Staurosporine
  • Tetraspanin 29
  • Tyrosine / metabolism

Substances

  • Alkaloids
  • Antibodies, Monoclonal
  • Antigens, CD
  • CD9 protein, human
  • Membrane Glycoproteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • Tetraspanin 29
  • phosphatidylinositol 3,4-diphosphate
  • Tyrosine
  • Protein Kinase C
  • Staurosporine