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Fig. 3 | Clinical and Translational Medicine

Fig. 3

From: PI3K inhibitors in thrombosis and cardiovascular disease

Fig. 3

The role of PI3Kβ in platelets. Class I PI3Kβ is considered a potential antithrombotic target due to its functional role downstream of various platelet receptors, and has received the most intense clinical interest of the PI3Ks so far in this setting. In particular, it plays a key role in sustaining integrin αIIbβ3 signalling to support stable thrombus formation under high shear, acting via the regulation of various cellular effectors which are responsive to its catalytic product, PtdIns(3,4,5)P3. PI3Kβ can receive activatory input via multiple interactions, including direct interaction of p85 with CBL downstream of αIIbβ3, association of the SH2 domains of p85 with phosphorylated tyrosines on receptors and adaptors downstream of Glycoprotein VI (GPVI), and interactions of p110β with RAC/CDC42 and the Gβγ subunits of activated heterotrimeric G proteins downstream of GPCRs such as P2Y12

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