Journal
BIOCHEMISTRY
Volume 40, Issue 3, Pages 791-800Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi001661b
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Funding
- NCI NIH HHS [CA34590, R01 CA034590-17, R01 CA034590-18, R01 CA034590, P30 CA068485, CA68485] Funding Source: Medline
- BLRD VA [IK6 BX005225] Funding Source: Medline
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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 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 beta -arrestin 1 but exhibit decreased binding to adaptin 2 alpha 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.
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