2. Academic Validation
  3. The hematopoietic isoform of Cas-Hef1-associated signal transducer regulates chemokine-induced inside-out signaling and T cell trafficking

The hematopoietic isoform of Cas-Hef1-associated signal transducer regulates chemokine-induced inside-out signaling and T cell trafficking

  • Immunity. 2006 Dec;25(6):907-18. doi: 10.1016/j.immuni.2006.09.014.
Adam G Regelmann 1,  Nichole M Danzl,  Celestine Wanjalla,  Konstantina Alexandropoulos
Affiliations

Affiliation

  • 1 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.
PMID: 17174122 DOI: 10.1016/j.immuni.2006.09.014
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.

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