First Author | Regelmann AG | Year | 2006 |
Journal | Immunity | Volume | 25 |
Issue | 6 | Pages | 907-18 |
PubMed ID | 17174122 | Mgi Jnum | J:116755 |
Mgi Id | MGI:3694989 | Doi | 10.1016/j.immuni.2006.09.014 |
Citation | Regelmann AG, et al. (2006) The hematopoietic isoform of Cas-Hef1-associated signal transducer regulates chemokine-induced inside-out signaling and T cell trafficking. Immunity 25(6):907-18 |
abstractText | 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. |