Regulation and roles of PI3Kbeta, a major actor in platelet signaling and functions.
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Gratacap MP, Guillermet-Guibert J, Martin V, Chicanne G, Tronchere H, Gaits-Iacovoni F, Payrastre B
Regulation and roles of PI3Kbeta, a major actor in platelet signaling and functions.
Adv Enzyme Regul. 2011;51(1):106-16. doi: 10.1016/j.advenzreg.2010.09.011. Epub 2010 Oct 28.
- PubMed ID
- 21035500 [ View in PubMed]
- Abstract
Phosphoinositide 3-kinases (PI3Ks) are important signaling enzymes involved in the regulation of a number of critical cell functions. Significant progress has been made during the last few years in defining the implication of individual PI3K isoforms. The role of the class IA PI3Kbeta in different cell types has only been recently uncovered by the use of isoform-selective inhibitors and the development of mouse models harboring p110beta catalytic subunit knock-out or germline knock-in of a kinase-dead allele of p110beta. Although it is classically admitted that class IA PI3Ks are activated by receptor tyrosine kinases through recruitment of the regulatory subunits to specific tyrosine phosphorylated motifs via their SH2 domains, PI3Kbeta is activated downstream of G protein-coupled receptors, and by co-operation between heterotrimeric G proteins and tyrosine kinases. PI3Kbeta has been extensively studied in platelets where it appears to play an important role downstream of ITAM signaling, G protein-coupled receptors and aIIbbeta3 integrin. Accordingly, mouse exhibiting p110beta inactivation selectively in megakaryocyte/platelets are resistant to thromboembolism induced by carotid injury. The present review summarizes recent data concerning the mechanisms of PI3Kbeta regulation and the roles of this PI3K isoform in blood platelet functions and other cell types.