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Curr Top Microbiol Immunol. 2010;346:203-24. doi: 10.1007/82_2010_61.

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

Author information

1
Australian Centre for Blood Diseases, Alfred Medical Research and Education Precinct (AMREP), Monash University, Melbourne, VIC, 3004, Australia. Shaun.Jackson@med.monash.edu.au

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.

PMID:
20517720
DOI:
10.1007/82_2010_61
[Indexed for MEDLINE]

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