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

G. H. Fan, W. Yang, X. J. Wang, Q. Qian, A. Richmond

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

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 β-arrestin 1 but continues to exhibit association with adaptin 2 α and β 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 Ca2+ 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 β-arrestin 1 but exhibit decreased binding to adaptin 2α and β. 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.

Original languageEnglish (US)
Pages (from-to)791-800
Number of pages10
JournalBiochemistry
Volume40
Issue number3
DOIs
StatePublished - Jan 23 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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