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.