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Volume 271, Number 43, Issue of October 25, 1996 pp. 26547-26553
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Dissociation of the _IIb3-Integrin by EGTA Stimulates the Tyrosine Kinase pp72^syk without Inducing Platelet Activation

(Received for publication, March 25, 1996, and in revised form, July 3, 1996)

From the Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, b. d. Universität München, Pettenkoferstrasse 9, 80336 Munich, Germany

Incubation of human platelets with EGTA under conditions that dissociate the _IIb3-integrin stimulated tyrosine phosphorylation of pp72^syk (6.8-fold) and of proteins of 62 (2.2-fold), 68 (2.5-fold) and 130 kDa (1.4-fold). Stimulation of tyrosine phosphorylation of pp72^syk was associated with an increase of pp72^syk kinase activity. In contrast to pp72^syk, tyrosine phosphorylation of the focal adhesion kinase pp125^FAK was not stimulated by EGTA. Preincubation of platelets with the monoclonal antibody P2, which binds to the _IIb3 complex and thus stabilizes it, strongly reduced the increase of tyrosine phosphorylation of pp72^syk, p62, and p68 induced by EGTA. The Y2/51 monoclonal antibody, which recognizes only the ₃ glycoprotein, did not inhibit the stimulation of protein tyrosine phosphorylation evoked by EGTA. Stimulation of tyrosine phosphorylation of pp72^syk, p62, p68, and p130 induced by EGTA was not observed in thrombasthenic platelets, which lack the _IIb3-integrin. The results indicate that the dissociation of the _IIb3 complex in intact platelets activates pp72^syk. The mechanism of activation was found to be insensitive to inhibition by cAMP and cGMP and only partially dependent on cytosolic Ca²⁺, suggesting a close functional coupling of _IIb3-integrin and pp72^syk. Since platelets retain their discoid shape after EGTA treatment, we further conclude that pp72^syk stimulation alone is not sufficient for platelet activation.

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