1. The hematopoietic isoform of Cas-Hef1-associated signal transducer regulates chemokine-induced inside-out signaling and T cell trafficking.
- Author
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Regelmann AG, Danzl NM, Wanjalla C, and Alexandropoulos K
- Subjects
- Adaptor Proteins, Signal Transducing immunology, Animals, Enzyme Activation physiology, Immunoblotting, Integrins immunology, Integrins metabolism, Mice, Mice, Inbred C57BL, Protein Isoforms immunology, Protein Isoforms metabolism, RNA, Small Interfering, Signal Transduction immunology, T-Lymphocytes immunology, rap1 GTP-Binding Proteins immunology, rap1 GTP-Binding Proteins metabolism, Adaptor Proteins, Signal Transducing metabolism, Cell Adhesion immunology, Chemotaxis, Leukocyte immunology, Models, Immunological, T-Lymphocytes metabolism
- Abstract
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.
- Published
- 2006
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