Chemokine signaling specificity: Essential role for the N-terminal domain of chemokine receptor

Gregory N. Prado, Katsutoshi Suetomi, David Shumate, Carrie Maxwell, Aishwarya Ravindran, Krishna Rajarathnam, Javier Navarro

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Chemokine IL-8 (CXCL8) binds to its cognate receptors CXCR1 and CXCR2 to induce inflammatory responses, wound healing, tumorogenesis, and neuronal survival. Here we identify the N-loop residues in IL-8 (H18 and F21) and the receptor N-termini as the major structural determinants regulating the rate of receptor internalization, which in turn controlled the activation profile of ERK1/2, a central component of the receptor/ERK signaling pathway that dictates signal specificity. Our data further support the idea that the chemokine receptor core acts as a plastic scaffold. Thus, the diversity and intensity of inflammatory and noninflammatory responses mediated by chemokine receptors appear to be primarily determined by the initial interaction between the receptor N-terminus and the N-loop of chemokines.

Original languageEnglish (US)
Pages (from-to)8961-8968
Number of pages8
JournalBiochemistry
Volume46
Issue number31
DOIs
StatePublished - Aug 7 2007

ASJC Scopus subject areas

  • Biochemistry

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