The Na+/H+ exchanger is phosphorylated in human platelets in response to activating agents.
alpha-Thrombin, phorbol esters (PMA) and 1,2-diacylglycerol (DAG), three activators of the amiloride-sensitive Na+/H+ exchange in human platelets, rapidly increase the intracellular pH and the level of phosphorylation of the Na+/H+ exchange protein (NHE1). This stimulatory effect is suppressed by staurosporine, a potent kinase inhibitor, and increased by okadaic acid, a potent inhibitor of phosphatase 1 and 2A. The modulations of NHE1 phosphorylation by these factors correlate well with their effects on platelet pH. Thus, we conclude that in platelets (i) Na+/H+ exchange is mediated by NHE1, and (ii) platelet activating agents stimulate NHE1 via the modulation of the kinase/phosphatase equilibrium.
Livne
A A
AA
C.N.R.S., Centre de Biochimie, Université de Nice, France.
Sardet
C
C
Pouyssegur
J
J
D000470:Alkaloids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood*; D004075:Diglycerides / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D054645:Protein Phosphatase 1; D017923:Sodium-Hydrogen Exchangers; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology*
C011439:1,2-diacylglycerol; D000470:Alkaloids; D002352:Carrier Proteins; D004075:Diglycerides; D004988:Ethers, Cyclic; D047428:Protein Kinase Inhibitors; D017923:Sodium-Hydrogen Exchangers; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D013917:Thrombin; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate