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 Elaine Hedin

Research output: Contribution to journalArticle

157 Citations (Scopus)

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 2006

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T-Cell Antigen Receptor
Mitogen-Activated Protein Kinases
T-Lymphocytes
ZAP-70 Protein-Tyrosine Kinase
CXCR4 Receptors
Transcription Factor AP-1
Chemotaxis
G-Protein-Coupled Receptors
Chemokines
Protein-Tyrosine Kinases
Immunity
Signal Transduction
Ions
Cytokines
Calcium
Gene Expression

Keywords

  • MOLIMMUNO
  • SIGNALING

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

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

CXCR4 Physically Associates with the T Cell Receptor to Signal in T Cells. / Kumar, Ashok; Humphreys, Troy D.; Kremer, Kimberly N.; Bramati, Patricia S.; Bradfield, Lavone; Edgar, Contessa E.; Hedin, Karen Elaine.

In: Immunity, Vol. 25, No. 2, 08.2006, p. 213-224.

Research output: Contribution to journalArticle

Kumar, A, Humphreys, TD, Kremer, KN, Bramati, PS, Bradfield, L, Edgar, CE & Hedin, KE 2006, 'CXCR4 Physically Associates with the T Cell Receptor to Signal in T Cells', Immunity, vol. 25, no. 2, pp. 213-224. https://doi.org/10.1016/j.immuni.2006.06.015
Kumar A, Humphreys TD, Kremer KN, Bramati PS, Bradfield L, Edgar CE et al. CXCR4 Physically Associates with the T Cell Receptor to Signal in T Cells. Immunity. 2006 Aug;25(2):213-224. https://doi.org/10.1016/j.immuni.2006.06.015
Kumar, Ashok ; Humphreys, Troy D. ; Kremer, Kimberly N. ; Bramati, Patricia S. ; Bradfield, Lavone ; Edgar, Contessa E. ; Hedin, Karen Elaine. / CXCR4 Physically Associates with the T Cell Receptor to Signal in T Cells. In: Immunity. 2006 ; Vol. 25, No. 2. pp. 213-224.
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