Chapter

Phosphoinositide 3-kinase in Health and Disease

Volume 346 of the series Current Topics in Microbiology and Immunology pp 203-224

Date:

PI 3-Kinase p110β Regulation of Platelet Integrin αIIbβ3

  • Shaun P. JacksonAffiliated withAustralian Centre for Blood Diseases, Alfred Medical Research and Education Precinct (AMREP), Monash University Email author 
  • , Simone M. SchoenwaelderAffiliated withAustralian Centre for Blood Diseases, Alfred Medical Research and Education Precinct (AMREP), Monash University

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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 Gi- and tyrosine kinase-coupled receptors. Functionally, inhibition of p110β kinase function leads to a marked defect in integrin αIIbβ3 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.