PI 3-Kinase p110β regulation of platelet integrin α(IIb)β3

Abstract

Hemopoietic cells express relatively high levels of the type I phosphoinositide (PI) 3-kinase isoforms, with p110δ and γ exhibiting specialized signaling functions in neutrophils, monocytes, mast cells, and lymphocytes. In platelets, p110β appears to be the dominant PI 3-kinase isoform regulating platelet activation, irrespective of the nature of the primary platelet activating stimulus. Based on findings with isoform-selective p110β pharmacological inhibitors and more recently with p110β-deficient platelets, p110β appears to primarily signal downstream of G(i)- and tyrosine kinase-coupled receptors. Functionally, inhibition of p110β kinase function leads to a marked defect in integrin α(IIb)β₃ adhesion and reduced platelet thrombus formation in vivo. This defect in platelet adhesive function is not associated with increased bleeding, suggesting that therapeutic targeting of p110β may represent a safe approach to reduce thrombotic complications in patients with cardiovascular disease.