The hematopoietic isoform of Cas-Hef1-associated signal transducer regulates chemokine-induced inside-out signaling and T cell trafficking.
Leukocyte migration and trafficking is dynamically regulated by various chemokine and adhesion molecules and is vital to the proper function of the immune system. We describe a role for the Cas and Hef-1-associated signal transducer in hematopoietic cells (Chat-H) as a critical regulator of T lymphocyte migration, by using lentivirus-mediated RNA interference (RNAi). Impaired migration of Chat-H-depleted cells coincided with defective inside-out signaling shown by diminished chemokine-induced activation of the Rap-1 GTPase and integrin-mediated adhesion. Localization of Chat-H to the plasma membrane, association with its binding partner Crk-associated substrate in lymphocytes (CasL), and Chat-H-mediated CasL serine-threonine phosphorylation were required for T cell migration. These results identify Chat-H as a critical signaling intermediate acting upstream of Rap1 to regulate chemokine-induced adhesion and migration.
Regelmann
Adam G
AG
The Integrated Program in Cellular, Molecular, and Biophysical Studies, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, New York 10032, USA.
Danzl
Nichole M
NM
Wanjalla
Celestine
C
Alexandropoulos
Konstantina
K
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004789:Enzyme Activation / Q000502:physiology; D015151:Immunoblotting; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D020827:rap1 GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D016023:Integrins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D020827:rap1 GTP-Binding Proteins