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

Sai J, Fan GH, Wang D, Richmond A
J Cell Sci. 2004 117 (Pt 23): 5489-96

PMID: 15479720 · PMCID: PMC2668248 · DOI:10.1242/jcs.01398

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.

MeSH Terms (25)

Amino Acid Motifs Blood Coagulation Factors cdc42 GTP-Binding Protein Cell Line Cell Polarity Chemotaxis DNA-Binding Proteins Endocytosis Fluorescence Resonance Energy Transfer Green Fluorescent Proteins Humans Ligands Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mutation Protein-Serine-Threonine Kinases Protein Structure, Tertiary Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt rac1 GTP-Binding Protein Receptors, Interleukin-8B Signal Transduction Transcription Factor AP-2 Transcription Factors Up-Regulation

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