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Identification of a motif in the carboxyl terminus of CXCR2 that is involved in adaptin 2 binding and receptor internalization.

Fan GH, Yang W, Wang XJ, Qian Q, Richmond A
Biochemistry. 2001 40 (3): 791-800

PMID: 11170396 · PMCID: PMC2664867 · DOI:10.1021/bi001661b

Agonist treatment of cells expressing the chemokine receptor, CXCR2, induces receptor phosphorylation and internalization through a dynamin-dependent mechanism. In the present study, we demonstrate that a carboxyl terminus-truncated mutant of CXCR2 (331T), which no longer undergoes agonist-induced phosphorylation, continues to undergo ligand-induced internalization in HEK293 cells. This mutant receptor exhibits reduced association with beta-arrestin 1 but continues to exhibit association with adaptin 2 alpha and beta subunits. Replacing Leu320-321 and/or Ile323-Leu324 with Ala (LL320,321AA, IL323,324AA, and LLIL320,321,323,324AAAA) in wild-type CXCR2 or 331T causes little change in ligand binding and signaling through Ca(2+) mobilization but greatly impairs the agonist-induced receptor sequestration and ligand-mediated chemotaxis. The LL320,321AA, IL323,324AA, and LLIL320,321,323,324AAAA mutants of CXCR2 exhibit normal binding to beta-arrestin 1 but exhibit decreased binding to adaptin 2alpha and beta. These data demonstrate a role for the LLKIL motif in the carboxyl terminus of CXCR2 in receptor internalization and cell chemotaxis and imply a role for adaptin 2 in the endocytosis of CXCR2.

MeSH Terms (23)

Adaptor Protein Complex alpha Subunits Adaptor Proteins, Vesicular Transport Amino Acid Motifs Amino Acid Sequence Animals Arrestins beta-Arrestin 1 beta-Arrestins Cell Line Chemotaxis Embryo, Mammalian Humans Kidney Ligands Membrane Proteins Molecular Sequence Data Mutagenesis, Site-Directed Peptide Fragments Rats Receptors, Interleukin-8B Signal Transduction Transfection Tumor Cells, Cultured

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