Gelkop Sigal, Babichev Yael, Kalifa Rachel, Tamir Ami, Isakov Noah
Department of Microbiology and Immunology, Faculty of Health Sciences, and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
Immunol Res. 2003;28(2):79-91. doi: 10.1385/IR:28:2:79.
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.
Crk衔接蛋白由Src同源2(SH2)结构域和SH3结构域组成,它们分别结合酪氨酸磷酸化肽段和富含多聚脯氨酸的基序。它们与包括淋巴细胞在内的不同细胞类型中的多种信号通路相关联,并且由于它们缺乏催化活性,许多关于Crk的研究旨在鉴定其结合伙伴并确定这些相互作用的生理意义。通过其SH2介导的与信号转导分子(如Cbl、ZAP-70、CasL和STAT5)的瞬时相互作用,发现Crk蛋白参与淋巴细胞激活的早期步骤。此外,Crk蛋白与介导细胞黏附的效应分子组成性相关,从而调节淋巴细胞渗出和向炎症部位的募集。本文描述了主要在淋巴细胞中进行的关于Crk的选定研究,并讨论了它们与Crk在调节淋巴细胞功能中的作用的潜在相关性。