Revised model of regulation of SFKs in the megakaryocyte lineage. (A) SFK activity is tightly regulated by the coordinated action of the tyrosine kinases Csk and Chk, the receptor-type tyrosine phosphatase PTPRJ, and SFKs themselves. Csk and Chk negatively regulate SFK activity, whereas PTPRJ and SFKs are dual positive and negative regulators of SFKs. (B) SFKs autoregulate their catalytic activity through the trans-phosphorylation of conserved tyrosine residues in the activation loop and C-terminal tail. (C) An equilibrium of different states of SFKs is established in resting and activated platelets through the interplay of these tyrosine kinases and phosphatase, as indicated. This is dependent on the concentrations, proximity, and catalytic activities of these enzymes.