The Hematopoietic Isoform of Cas-Hef1-Associated Signal Transducer Regulates Chemokine-Induced Inside-Out Signaling and T Cell Trafficking

Adam G. Regelmann; Nichole M. Danzl; Celestine Wanjalla; Konstantina Alexandropoulos

doi:10.1016/j.immuni.2006.09.014

The Hematopoietic Isoform of Cas-Hef1-Associated Signal Transducer Regulates Chemokine-Induced Inside-Out Signaling and T Cell Trafficking

Adam G. Regelmann, Nichole M. Danzl, Celestine Wanjalla, Konstantina Alexandropoulos

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

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.

Original language	English
Pages (from-to)	907-918
Number of pages	12
Journal	Immunity
Volume	25
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2006.09.014
State	Published - Dec 2006
Externally published	Yes

Keywords

MOLIMMUNO
SIGNALING

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title = "The Hematopoietic Isoform of Cas-Hef1-Associated Signal Transducer Regulates Chemokine-Induced Inside-Out Signaling and T Cell Trafficking",

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.",

keywords = "MOLIMMUNO, SIGNALING",

author = "Regelmann, {Adam G.} and Danzl, {Nichole M.} and Celestine Wanjalla and Konstantina Alexandropoulos",

note = "Funding Information: The authors would like to thank C. Dillon (MIT) for the lentiviral system; S. Goff (Columbia) for the pHit123 vector; K. Gordon for help with FACS; and A. Pernis, Y. Zou, H. Gu, C. Roman, and W. Regelmann for their careful review of this manuscript. We would also like to thank B. Diamond, T. Wang, and A. Kalkandis for their support. This work was supported by Columbia University's MD/PhD program and by the National Institute of Allergy and Infectious Disease (NIAID) Grant RO1 AI49387-01. ",

year = "2006",

month = dec,

doi = "10.1016/j.immuni.2006.09.014",

language = "English",

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AU - Regelmann, Adam G.

AU - Danzl, Nichole M.

AU - Wanjalla, Celestine

AU - Alexandropoulos, Konstantina

N1 - Funding Information: The authors would like to thank C. Dillon (MIT) for the lentiviral system; S. Goff (Columbia) for the pHit123 vector; K. Gordon for help with FACS; and A. Pernis, Y. Zou, H. Gu, C. Roman, and W. Regelmann for their careful review of this manuscript. We would also like to thank B. Diamond, T. Wang, and A. Kalkandis for their support. This work was supported by Columbia University's MD/PhD program and by the National Institute of Allergy and Infectious Disease (NIAID) Grant RO1 AI49387-01.

PY - 2006/12

Y1 - 2006/12

N2 - 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.

AB - 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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AN - SCOPUS:33845490019

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The Hematopoietic Isoform of Cas-Hef1-Associated Signal Transducer Regulates Chemokine-Induced Inside-Out Signaling and T Cell Trafficking

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Keywords

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