Department of Medicine, Division of Clinical Immunology, The Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Immunol Rev. 2009 Nov;232(1):160-74. doi: 10.1111/j.1600-065X.2009.00831.x.
The Cas family of proteins consists of at least four members implicated in the regulation of diverse cellular processes such as cell proliferation, adhesion, motility, and cancer cell metastasis. Cas family members have conserved C-termini that mediate constitutive heterotypic interactions with members of a different group of proteins, the NSP family. Both the Cas and NSP proteins have conserved domains that mediate protein-protein interactions with other cytoplasmic intermediates. Signaling modules assembled by these proteins in turn regulate signal transduction downstream of a variety of receptors including integrin, chemokine, and antigen receptors. T lymphocytes express the NSP protein NSP3/Chat-H and the Cas protein Hef1/CasL, which are found in a constitutive complex in naive T cells. We recently showed that Chat-H and Hef1/CasL regulate integrin-mediated adhesion and promote T-cell migration and trafficking downstream of activated chemokine receptors. It is currently unclear if the Chat-H/CasL module also plays a role in antigen receptor signaling. Here we review our current knowledge of how Chat-H and Hef1/CasL regulate T-cell physiology and whether this protein complex plays a functional role downstream of T-cell receptor activation.
Cas 蛋白家族至少由四个成员组成，这些成员参与调节多种细胞过程，如细胞增殖、黏附、运动和癌细胞转移。Cas 家族成员具有保守的 C 末端，介导与不同蛋白家族成员（NSP 家族）的组成型异质相互作用。Cas 和 NSP 蛋白都具有保守结构域，介导与其他细胞质中间产物的蛋白-蛋白相互作用。这些蛋白质组装的信号模块依次调节各种受体（包括整合素、趋化因子和抗原受体）下游的信号转导。T 淋巴细胞表达 NSP 蛋白 NSP3/Chat-H 和 Cas 蛋白 Hef1/CasL，它们在幼稚 T 细胞中存在于组成型复合物中。我们最近表明，Chat-H 和 Hef1/CasL 调节整合素介导的黏附，并促进激活趋化因子受体后的 T 细胞迁移和运输。目前尚不清楚 Chat-H/CasL 模块是否也在抗原受体信号转导中发挥作用。在这里，我们回顾了我们目前对 Chat-H 和 Hef1/CasL 如何调节 T 细胞生理学的了解，以及该蛋白复合物在 T 细胞受体激活下游是否发挥功能作用。
