Fig. 7

Proposed model for the dual role of Dab2 phosphorylations in platelet activation. Two pools of Dab2 are present in human platelets. PKC-mediated Dab2 Ser723 phosphorylation mainly distributed in the cytosolic fraction causes the dissociation of Dab2-CIN85 protein complex upon agonist-stimulated integrin inside-out signaling. The molecular consequences for the dissociation of Dab2-CIN85 protein complex is related to ADP release, integrin αIIbβ3 activation, fibrinogen binding and platelet aggregation. Activation of the Src-PKC signaling axis and PLD underlying integrin outside-in signaling causes Dab2-Ser24 phosphorylation, which is mainly distributed in the membrane fraction and subsequently regulates platelet spreading on fibrinogen. PP2 (a Src inhibitor), staurosporine (a PKC inhibitor), VU0155069 (a PLD1 inhibitor) and R11-S24 peptide suppress Dab2-Ser24 phosphorylation