Figure 5
Early αIIbβ3-mediated outside-in signaling. (A) Schematic representation of select signaling intermediates in αIIbβ3-induced lamellipodia formation and spreading under static conditions.2 Fibrinogen binding to αIIbβ3 induces phosphorylation of Src family kinases and Syk, which in turn phosphorylate ADAP and SLP-76 to promote their association. ADAP is shown constitutively associated with Fyn (green oval) and SKAP-HOM (black oval). Phosphorylation of SLP-76 at tyrosines 112 and 128 induces recruitment and phosphorylation of Vav1,40,53 thereby activating its guanine nucleotide exchange function to activate Rac1 and promote lamellipodia formation. The role of ADAP in this pathway is shown as “??” in figure. (B) Immunofluorescent staining of c-Src pTyr-418 in perfusion-fixed ADAP+/+ (left) and ADAP−/− platelets (middle) adhering onto fibrinogen under flow. Note regular intervals of c-Src pTyr-418 staining along filopodia (arrows). Staining with a control rabbit IgG antibody was minimal (right). (C) Quantification of average c-Src pTyr-418 fluorescence per platelet, representing an average of 3 experiments ± SEM.

Early αIIbβ3-mediated outside-in signaling. (A) Schematic representation of select signaling intermediates in αIIbβ3-induced lamellipodia formation and spreading under static conditions. Fibrinogen binding to αIIbβ3 induces phosphorylation of Src family kinases and Syk, which in turn phosphorylate ADAP and SLP-76 to promote their association. ADAP is shown constitutively associated with Fyn (green oval) and SKAP-HOM (black oval). Phosphorylation of SLP-76 at tyrosines 112 and 128 induces recruitment and phosphorylation of Vav1,40,53  thereby activating its guanine nucleotide exchange function to activate Rac1 and promote lamellipodia formation. The role of ADAP in this pathway is shown as “??” in figure. (B) Immunofluorescent staining of c-Src pTyr-418 in perfusion-fixed ADAP+/+ (left) and ADAP−/− platelets (middle) adhering onto fibrinogen under flow. Note regular intervals of c-Src pTyr-418 staining along filopodia (arrows). Staining with a control rabbit IgG antibody was minimal (right). (C) Quantification of average c-Src pTyr-418 fluorescence per platelet, representing an average of 3 experiments ± SEM.

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