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JCS ePress online publication date 12 Oct 2004
doi: 10.1242/jcs.01398

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Research Article

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, and Ann Richmond*
* Author for correspondence (e-mail: ann.richmond{at}vanderbilt.edu)

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.


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