Regulation of T-lymphocyte physiology by the Chat-H/CasL adapter complex.
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.
Alexandropoulos
Konstantina
K
Department of Medicine, Division of Clinical Immunology, The Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. k.alexandropoulos@mssm.edu
Regelmann
Adam G
AG
D000818:Animals; D002448:Cell Adhesion; D050719:Crk-Associated Substrate Protein / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D036904:Leukocyte Rolling; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D055503:Protein Multimerization; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D009419:Nerve Tissue Proteins; D011948:Receptors, Antigen, T-Cell; C489914:Rtn1 protein, mouse