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

@article{citeulike:3042877, 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 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.}, address = {Veterans Affairs Medical Center, Nashville, Tennessee 37212-2637, USA.}, author = {Fan, G. H. and Yang, W. and Wang, X. J. and Qian, Q. and Richmond, A.}, citeulike-article-id = {3042877}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11170396}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11170396}, day = {23}, issn = {0006-2960}, journal = {Biochemistry}, keywords = {ap-2, cxcr2}, month = {January}, number = {3}, pages = {791--800}, posted-at = {2008-07-25 16:13:14}, priority = {2}, title = {Identification of a motif in the carboxyl terminus of CXCR2 that is involved in adaptin 2 binding and receptor internalization.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11170396}, volume = {40}, year = {2001} }

TY - JOUR ID - citeulike:3042877 L3 - citeulike-article-id:3042877 N2 - 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. IS - 3 JF - Biochemistry SN - 0006-2960 AD - Veterans Affairs Medical Center, Nashville, Tennessee 37212-2637, USA. EP - 800 TI - Identification of a motif in the carboxyl terminus of CXCR2 that is involved in adaptin 2 binding and receptor internalization. VL - 40 SP - 791 KW - ap-2 KW - cxcr2 AU - Fan, GH AU - Yang, W AU - Wang, XJ AU - Qian, Q AU - Richmond, A PY - 2001/01/23/ UR - http://view.ncbi.nlm.nih.gov/pubmed/11170396 ER -