CXCR4 Physically Associates with the T Cell Receptor to Signal in T Cells

Ashok Kumar, Troy D. Humphreys, Kimberly N. Kremer, Patricia S. Bramati, Lavone Bradfield, Contessa E. Edgar, Karen E. Hedin

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

SDF-1α (CXCL12) signaling via its receptor, CXCR4, stimulates T cell chemotaxis and gene expression. The ZAP-70 tyrosine kinase critically mediates SDF-1α-dependent migration and prolonged ERK mitogen-activated protein (MAP) kinase activation in T cells. However, the molecular mechanism by which CXCR4 or other G protein-coupled receptors activate ZAP-70 has not been characterized. Here we show that SDF-1α stimulates the physical association of CXCR4 and the T cell receptor (TCR) and utilizes the ZAP-70 binding ITAM domains of the TCR for signal transduction. This pathway is responsible for several of the effects of SDF-1α on T cells, including prolonged ERK MAP kinase activity, increased intracellular calcium ion concentrations, robust AP-1 transcriptional activity, and SDF-1α costimulation of cytokine secretion. These results suggest new paradigms for understanding the effects of SDF-1α and other chemokines on immunity.

Original languageEnglish (US)
Pages (from-to)213-224
Number of pages12
JournalImmunity
Volume25
Issue number2
DOIs
StatePublished - Aug 1 2006

Keywords

  • MOLIMMUNO
  • SIGNALING

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Kumar, A., Humphreys, T. D., Kremer, K. N., Bramati, P. S., Bradfield, L., Edgar, C. E., & Hedin, K. E. (2006). CXCR4 Physically Associates with the T Cell Receptor to Signal in T Cells. Immunity, 25(2), 213-224. https://doi.org/10.1016/j.immuni.2006.06.015