A role for a RhoA/ROCK/LIM-kinase pathway in the regulation of cytotoxic lymphocytes

Zhenkun Lou, Daniel D Billadeau, D. N. Savoy, R. A. Schoon, P. J. Leibson

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Polarization of lipid rafts and granules to the site of target contact is required for the development of cell-mediated killing by cytotoxic lymphocytes. We have previously shown that these events require the activation of proximal protein tyrosine kinases. However, the downstream intracellular signaling molecules involved in the development of cell-mediated cytotoxicity remain poorly defined. We report here that a RhoA/ROCK/LIM-kinase axis couples the receptor-initiated protein tyrosine kinase activation to the reorganization of the actin cytoskeleton required for the polarization of lipid rafts and the subsequent generation of cell-mediated cytotoxicity. Pharmacologic and genetic interruption of any element of this RhoA/ROCK/LIM-kinase pathway inhibits both the accumulation of F-actin and lipid raft polarization to the site of target contact and the subsequent delivery of the lethal hit. These data define a specialized role for a RhoA→ROCK→LIM-kinase pathway in cytotoxic lymphocyte activation.

Original languageEnglish (US)
Pages (from-to)5749-5757
Number of pages9
JournalJournal of Immunology
Volume167
Issue number10
StatePublished - Nov 15 2001

Fingerprint

Lim Kinases
Lymphocytes
Lipids
Receptor Protein-Tyrosine Kinases
Lymphocyte Activation
Actin Cytoskeleton
Protein-Tyrosine Kinases
Actins
Phosphotransferases

ASJC Scopus subject areas

  • Immunology

Cite this

A role for a RhoA/ROCK/LIM-kinase pathway in the regulation of cytotoxic lymphocytes. / Lou, Zhenkun; Billadeau, Daniel D; Savoy, D. N.; Schoon, R. A.; Leibson, P. J.

In: Journal of Immunology, Vol. 167, No. 10, 15.11.2001, p. 5749-5757.

Research output: Contribution to journalArticle

Lou, Zhenkun ; Billadeau, Daniel D ; Savoy, D. N. ; Schoon, R. A. ; Leibson, P. J. / A role for a RhoA/ROCK/LIM-kinase pathway in the regulation of cytotoxic lymphocytes. In: Journal of Immunology. 2001 ; Vol. 167, No. 10. pp. 5749-5757.
@article{797c66f6b5ca4189bc40bac831e10bea,
title = "A role for a RhoA/ROCK/LIM-kinase pathway in the regulation of cytotoxic lymphocytes",
abstract = "Polarization of lipid rafts and granules to the site of target contact is required for the development of cell-mediated killing by cytotoxic lymphocytes. We have previously shown that these events require the activation of proximal protein tyrosine kinases. However, the downstream intracellular signaling molecules involved in the development of cell-mediated cytotoxicity remain poorly defined. We report here that a RhoA/ROCK/LIM-kinase axis couples the receptor-initiated protein tyrosine kinase activation to the reorganization of the actin cytoskeleton required for the polarization of lipid rafts and the subsequent generation of cell-mediated cytotoxicity. Pharmacologic and genetic interruption of any element of this RhoA/ROCK/LIM-kinase pathway inhibits both the accumulation of F-actin and lipid raft polarization to the site of target contact and the subsequent delivery of the lethal hit. These data define a specialized role for a RhoA→ROCK→LIM-kinase pathway in cytotoxic lymphocyte activation.",
author = "Zhenkun Lou and Billadeau, {Daniel D} and Savoy, {D. N.} and Schoon, {R. A.} and Leibson, {P. J.}",
year = "2001",
month = "11",
day = "15",
language = "English (US)",
volume = "167",
pages = "5749--5757",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - A role for a RhoA/ROCK/LIM-kinase pathway in the regulation of cytotoxic lymphocytes

AU - Lou, Zhenkun

AU - Billadeau, Daniel D

AU - Savoy, D. N.

AU - Schoon, R. A.

AU - Leibson, P. J.

PY - 2001/11/15

Y1 - 2001/11/15

N2 - Polarization of lipid rafts and granules to the site of target contact is required for the development of cell-mediated killing by cytotoxic lymphocytes. We have previously shown that these events require the activation of proximal protein tyrosine kinases. However, the downstream intracellular signaling molecules involved in the development of cell-mediated cytotoxicity remain poorly defined. We report here that a RhoA/ROCK/LIM-kinase axis couples the receptor-initiated protein tyrosine kinase activation to the reorganization of the actin cytoskeleton required for the polarization of lipid rafts and the subsequent generation of cell-mediated cytotoxicity. Pharmacologic and genetic interruption of any element of this RhoA/ROCK/LIM-kinase pathway inhibits both the accumulation of F-actin and lipid raft polarization to the site of target contact and the subsequent delivery of the lethal hit. These data define a specialized role for a RhoA→ROCK→LIM-kinase pathway in cytotoxic lymphocyte activation.

AB - Polarization of lipid rafts and granules to the site of target contact is required for the development of cell-mediated killing by cytotoxic lymphocytes. We have previously shown that these events require the activation of proximal protein tyrosine kinases. However, the downstream intracellular signaling molecules involved in the development of cell-mediated cytotoxicity remain poorly defined. We report here that a RhoA/ROCK/LIM-kinase axis couples the receptor-initiated protein tyrosine kinase activation to the reorganization of the actin cytoskeleton required for the polarization of lipid rafts and the subsequent generation of cell-mediated cytotoxicity. Pharmacologic and genetic interruption of any element of this RhoA/ROCK/LIM-kinase pathway inhibits both the accumulation of F-actin and lipid raft polarization to the site of target contact and the subsequent delivery of the lethal hit. These data define a specialized role for a RhoA→ROCK→LIM-kinase pathway in cytotoxic lymphocyte activation.

UR - http://www.scopus.com/inward/record.url?scp=0035889929&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035889929&partnerID=8YFLogxK

M3 - Article

C2 - 11698448

AN - SCOPUS:0035889929

VL - 167

SP - 5749

EP - 5757

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -