- The Crk adapter proteins consist of Src homology 2 (SH2) SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and polyproline-rich motives, respectively. They are linked to multiple signaling pathways in different cell types, including lymphocytes, and because of their lack of catalytic activity, many studies on Crk were aimed at the identification of their binding partners and determination of the physiologic meaning of these interactions. Crk proteins were found to be involved in the early steps of lymphocyte activation through their SH2-mediated transient interaction with signal-transducing molecules, such as Cbl, ZAP-70, CasL, and STAT5. In addition, Crk proteins are constitutively associated with effector molecules that mediate cell adhesion and thereby regulate lymphocyte extravasation and recruitment to sites of inflammation. This article describes selected studies of Crk, performed predominantly in lymphocytes, and discusses their potential relevance to the role of Crk in the regulation of lymphocyte functions.