Signaling responses to alkyllysophosphatidic acid: the activation of phospholipases A2 and C and protein tyrosine phosphorylation in human platelets

Archives of Biochemistry and Biophysics
S SvetlovM S Olson

Abstract

The profile of biochemical responses following stimulation of human platelets with 1-alkyl-2-lyso-sn-glycero-3-phosphate (ALPA), a derivative of platelet-activating factor (PAF), was investigated. In the presence of extracellular Ca2+, ALPA evoked a dose-dependent increase and sustained elevation of the intracellular free Ca2+ concentration and stimulated the formation of phosphatidic acid. Platelets released free [3H]arachidonic and [3H]oleic acid at maximal rates between 5 and 15 s following ALPA stimulation. However, in platelets labeled with myo-[3H]inositol, ALPA induced [3H]phosphoinositide breakdown and formation of [3H]inositol phosphates with slower kinetics. Intracellular Ca2+ mobilization and the release of free fatty acids and inositol phosphates were not inhibited by pretreatment of platelets with pertussis toxin (PTX) or the PAF receptor antagonist WEB 2086. Following platelet stimulation with ALPA, tyrosine phosphorylation of proteins with apparent molecular masses of 65-95, 110-130, and 145-170 kDa was increased in a time-dependent manner, while phosphorylation of 40- to 45-kDa proteins was decreased. One of the platelet proteins phosphorylated on tyrosine residues in response to ALPA was found to be PLC-gamma1....Continue Reading

Citations

Jun 27, 2002·The Journal of Biological Chemistry·Yuhuan XieKathryn E Meier
May 29, 1998·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·T Hunter
Jul 24, 2004·Seminars in Cell & Developmental Biology·Saubhik SenguptaYan Xu

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