QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 12 October 2004
doi: 10.1242/jcs.01398

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.01398v1 117/23/5489    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sai, J. Articles by Richmond, A. Search for Related Content PubMed PubMed Citation Articles by Sai, J. Articles by Richmond, A.

The C-terminal domain LLKIL motif of CXCR2 is required for ligand-mediated polarization of early signals during chemotaxis

Department of Veteran Affairs, Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

^* Author for correspondence (e-mail: ann.richmond{at}vanderbilt.edu)

Accepted 6 July 2004

HEK293 cells expressing wild-type CXCR2 recruit PH-Akt-GFP to the leading edge of the cell in response to chemokine. However, in cells expressing mutant CXCR2 defective in AP-2 and HIP binding, i.e. with a mutation in the LLKIL motif, PH-Akt-GFP does not localize to the leading edge in response to ligand. Inhibition of Akt/PKB by transfection of HEK 293 cells with a dominant negative (kinase defective) Akt/PKB inhibits CXCR2 mediated chemotaxis. FRET analysis reveals that membrane-bound activated Cdc42 and Rac1 localize to the leading edge of cells expressing wild-type CXCR2 receptor, but not in cells expressing mutant CXCR2. By contrast, when the activation of Cdc42 and Rac1 are monitored by affinity precipitation assay, cells expressing either wild-type or LLKIL mutant receptors show equivalent ligand induction. Altogether, these data suggest that restricted localized activation of Akt/PKB, Rac1 and Cdc42 is crucial for chemotactic responses and that events mediated by the LLKIL motif are crucial for chemotaxis.

Key words: CXCR2, AP-2, Internalization, Chemotaxis, PH-Akt-GFP, FRET

This article has been cited by other articles:

				C. Cataisson, R. Ohman, G. Patel, A. Pearson, M. Tsien, S. Jay, L. Wright, H. Hennings, and S. H. Yuspa Inducible Cutaneous Inflammation Reveals a Protumorigenic Role for Keratinocyte CXCR2 in Skin Carcinogenesis Cancer Res., January 1, 2009; 69(1): 319 - 328. [Abstract] [Full Text] [PDF]

				C. Otero, P. S. Eisele, K. Schaeuble, M. Groettrup, and D. F. Legler Distinct motifs in the chemokine receptor CCR7 regulate signal transduction, receptor trafficking and chemotaxis J. Cell Sci., August 15, 2008; 121(16): 2759 - 2767. [Abstract] [Full Text] [PDF]

				Y. Yu, Y. Su, S. R. Opalenik, T. Sobolik-Delmaire, N. F. Neel, S. Zaja-Milatovic, S. T. Short, J. Sai, and A. Richmond Short tail with skin lesion phenotype occurs in transgenic mice with keratin-14 promoter-directed expression of mutant CXCR2 J. Leukoc. Biol., August 1, 2008; 84(2): 406 - 419. [Abstract] [Full Text] [PDF]

				J. Sai, G. Walker, J. Wikswo, and A. Richmond The IL Sequence in the LLKIL Motif in CXCR2 Is Required for Full Ligand-induced Activation of Erk, Akt, and Chemotaxis in HL60 Cells J. Biol. Chem., November 24, 2006; 281(47): 35931 - 35941. [Abstract] [Full Text] [PDF]

				Y. Ueda, N. F. Neel, E. Schutyser, D. Raman, and A. Richmond Deletion of the COOH-Terminal Domain of CXC Chemokine Receptor 4 Leads to the Down-regulation of Cell-to-Cell Contact, Enhanced Motility and Proliferation in Breast Carcinoma Cells Cancer Res., June 1, 2006; 66(11): 5665 - 5675. [Abstract] [Full Text] [PDF]