Platelet aggregation is perhaps the most dramatic of the cellular interactions occurring within the vasculature. Stimulation of platelets by thrombin, collagen, or ADP causes, within seconds, a burst of actin polymerization, a change in platelet shape from a disc to an irregular sphere with numerous filopodia, and a change in the membrane surface so that platelets aggregate. When this occurs in response to external trauma, platelet aggregation initiates hemostasis to stop bleeding. However, in response to aberrations within the vasculature such as an atherosclerotic; lesion, such aggregates form a thrombus that may induce life-threatening ischemic events such as infarction, angina, and stroke.

The membrane protein mediating platelet aggregation is the glycoprotein (GP) Ilb-llla complex (also termed aI& in the integrin nomenclature; Kieffer and Phillips, 1990). GPllb-llla is the most abundant of the platelet integrins and is restricted in distribution to platelets and cells of megakaryoblastic potential. On unstimulated platelets, GPllb-llla is randomly dispersed on the surface and is capable of recognizing only immobilized fibrinogen. In response to platelet stimulation, however, GPllb-llla becomes a receptor for several soluble adhesive proteins, the binding of which is mediated in part by the Arg-Gly-Asp (RGD) recognition sequence, inducing GPllb-llla to form patches on the platelet surface. Binding of two of these proteins, fibrinogen and von Willebrand factor, causes platelets to aggregate. Inherited deficiencies of GPllb-llla content or function have been described (termed Glanzmann’s thrombasthenia) and are characterized by platelets that do not bind adhesive proteins and therefore fail to aggregate, resulting in a life-long bleeding diathesis. Here we review recent findings concerning the characterization of adhesive protein binding sites on GPllb-llla and the functional responses of GPllb-llla to receptor occupancy. The themes to be developed are twofold. First, while it is well known that platelet stimulation enhances the adhesive function of GPllb-llla, there is emerging evidence that the binding of adhesive proteins to unactivated GPllb-llla may in turn stimulate platelets and/or activate GPllb-llla and thus play a role in aggregate formation (see Figure 1). Second, while GPllb-llla and many other integrins bind the RGD sequence on adhesive proteins, there are unique aspects to the binding of these recognition sequences to GPllb-llla (see Table 1). This review was prompted by the recent, novel finding that peptides containing GPllb-llla recognition sequences directly activate the adhesive protein binding function of GPllb-llla (Du et al., 1991).