Role of clathrin-mediated endocytosis in CXCR2 sequestration, resensitization, and signal transduction

Wei Yang, Dingzhi Wang, Ann Richmond

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

CXCR2 is a seven-transmembrane receptor that transduces intracellular signals in response to the chemokines interleukin-8, melanoma growth- stimulatory activity/growth-regulatory protein, and other ELR motif- containing CXC chemokines by coupling to heterotrimeric GTP-binding proteins. In this study, we explored the mechanism responsible for ligand-induced CXCR2 endocytosis. Here, we demonstrate that dynamin, a component of clathrin- mediated endocytosis, is essential for CXCR2 endocytosis and resensitization. In HEK293 cells, dynamin I K44A, a dominant-negative mutant of dynamin that inhibits the clathrin-mediated endocytosis, blocks the ligand-stimulated CXCR2 sequestration. Furthermore, co-expression of dynamin I K44A significantly delays dephosphorylation of CXCR2 after ligand stimulation, suggesting that clathrin-mediated endocytosis plays an important role in receptor dephosphorylation and resensitization. In addition, ligand-mediated receptor down-regulation is attenuated when receptor internalization is inhibited by dynamin I K44A. Interestingly, inhibition of receptor endocytosis by dynamin I K44A does not affect the CXCR2-mediated stimulation of mitogen-activated protein kinase. Most significantly, our data indicate that the ligand-stimulated receptor endocytosis is required for CXCR2- mediated chemotaxis in HEK293 cells. Taken together, our findings suggest that clathrin-mediated CXCR2 internalization is crucial for receptor endocytosis, resensitization, and chemotaxis.

Original languageEnglish (US)
Pages (from-to)11328-11333
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number16
DOIs
StatePublished - Apr 16 1999
Externally publishedYes

Fingerprint

Dynamin I
Signal transduction
Clathrin
Endocytosis
Dynamins
Signal Transduction
Ligands
HEK293 Cells
Chemotaxis
CXC Chemokines
Heterotrimeric GTP-Binding Proteins
Mitogen-Activated Protein Kinases
Interleukin-8
Chemokines
Growth
Melanoma
Down-Regulation
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Role of clathrin-mediated endocytosis in CXCR2 sequestration, resensitization, and signal transduction. / Yang, Wei; Wang, Dingzhi; Richmond, Ann.

In: Journal of Biological Chemistry, Vol. 274, No. 16, 16.04.1999, p. 11328-11333.

Research output: Contribution to journalArticle

Yang, Wei ; Wang, Dingzhi ; Richmond, Ann. / Role of clathrin-mediated endocytosis in CXCR2 sequestration, resensitization, and signal transduction. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 16. pp. 11328-11333.
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