© 1998 American Heart Association, Inc.
Original Contributions |
Differential Involvement of Tyrosine and Serine/Threonine Kinases in Platelet Integrin 
IIbß3 Exposure
From the Department of Haematology, University Hospital Utrecht, and the Institute for Biomembranes, Utrecht University, Utrecht, the Netherlands.
Correspondence to Dr J.W.N. Akkerman, Department of Haematology, University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands. E-mail j.w.n.akkerman{at}lab.azu.nl
Abstract—The relative
contributions of protein tyrosine kinases (PTKs) and protein kinase C
isoenzymes (PKCs), a family of serine/threonine kinases, in integrin
IIbß3 (glycoprotein IIb/IIIa)
exposure are the subject of much controversy. In the present study
we measured the effect of the PTK inhibitor herbimycin A
and the PKC inhibitor bisindolylmaleimide I on
125I-fibrinogen binding to
IIbß3 and on aggregation/secretion induced
by different agonists. Dose-response studies showed complete inhibition
of IIbß3 exposure by 30 µmol/L (ADP
stimulation) and 35 to 40 µmol/L (-thrombin stimulation)
herbimycin A. In contrast, inhibition of exposure by
bisindolylmaleimide I varied from none (for ADP and
epinephrine), to 30% (for platelet-activating factor), and
to 
80% (for -thrombin). Studies with a submaximal dose of
herbimycin A (50% inhibition of the ADP-response) and a maximal
dose of bisindolylmaleimide I showed that optical aggregation had a
similar sensitivity to the inhibitors as
IIbß3 exposure with minimal interference
by secreted ADP. Thus, the relative contributions of tyrosine and
serine/threonine kinases in IIbß3 exposure
and aggregation differ among the different agonists, with an exclusive
role for PTKs in ADP- and epinephrine-induced responses and a
role for both PTKs and PKCs in responses induced by
platelet-activating factor and -thrombin.
Key Words: integrin IIbß3 • fibrinogen binding • aggregation • human platelets • protein phosphorylation
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