Figure 7.

Regulation of platelet SFKs by the kinase Csk and the phosphatase CD148. (A) Csk and CD148 are the main regulators of SFK activity in platelets and impact different platelet signaling pathways. Csk inhibits SFK activity, whereas CD148 activates SFKs, but it can also inhibit SFK activity under conditions that have yet to be defined. In turn, SFKs regulate ITAM, hemi-ITAM, integrin, ITIM, and P2Y₁₂ receptor signaling pathways. See also Figures 4B and 5Dii. (B) Postactivated platelets. Platelets possess remarkable positive-feedback pathways (eg, ADP, TXA2), which further enhance platelet activation. Platelet activation is followed by receptor proteolysis or internalization, de novo protein synthesis, and downregulation of tyrosine phosphorylation pathways by ITIM-containing receptors and phosphatases. Csk KO and DKO platelets have increased SFK activity, which results in reduced expression of the platelet activating receptors GPVI and CLEC-2, increased expression of the ITIM-containing receptor G6b-B, and increased ITIM signaling, suggesting that these platelets exist in a postactivated state. Professional illustration by Patrick Lane, ScEYEnce Studios.