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

Jiqing Sai, Guo Huang Fan, Dingzhi Wang, Ann Richmond

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5489-5496
Number of pages8
JournalJournal of Cell Science
Volume117
Issue number23
DOIs
StatePublished - Nov 1 2004

Keywords

  • AP-2
  • CXCR2
  • Chemotaxis
  • FRET
  • Internalization
  • PH-Akt-GFP

ASJC Scopus subject areas

  • Cell Biology

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