| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
/CXCL12 Chemokine1
Departments of Surgery and Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905
Stimulation of T lymphocytes with the ligand for the CXCR4 chemokine receptor stromal cell-derived factor-1
(SDF-1/CXCL12), results in prolonged activation of the extracellular signal-regulated kinases (ERK) ERK1 and ERK2. Because SDF-1 is unique among several chemokines in its ability to stimulate prolonged ERK activation, this pathway is thought to mediate special functions of SDF-1 that are not shared with other chemokines. However, the molecular mechanisms of this response are poorly understood. In this study we show that SDF-1 stimulation of prolonged ERK activation in Jurkat T cells requires both the ZAP-70 tyrosine kinase and the Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) scaffold protein. This pathway involves ZAP-70-dependent tyrosine phosphorylation of SLP-76 at one or more of its tyrosines, 113, 128, and 145. Because TCR activates ERK via SLP-76-mediated activation of the linker of activated T cells (LAT) scaffold protein, we examined the role of LAT in SDF-1-mediated ERK activation. However, neither the SLP-76 proline-rich domain that links to GADS and LAT, nor LAT, itself are required for SDF-1 to stimulate SLP-76 tyrosine phosphorylation or to activate ERK. Together, our results describe the distinct mechanism by which SDF-1 stimulates prolonged ERK activation in T cells and indicate that this pathway is specific for cells expressing both ZAP-70 and SLP-76.
This article has been cited by other articles:
|
|
 |
|
  M. C. Ghosh, D. Baatar, G. Collins, A. Carter, F. Indig, A. Biragyn, and D. D. Taub Dexamethasone augments CXCR4-mediated signaling in resting human T cells via the activation of the Src kinase Lck Blood, January 15, 2009; 113(3): 575 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Shahabi, K. McAllen, and B. M. Sharp Stromal cell-derived factor 1-{alpha} (SDF)-induced human T cell chemotaxis becomes phosphoinositide 3-kinase (PI3K)-independent: role of PKC-{theta} J. Leukoc. Biol., March 1, 2008; 83(3): 663 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Park, I. Park, D. Lee, Y. B. Choi, H. Lee, and Y. Yun The adaptor protein Lad associates with the G protein {beta} subunit and mediates chemokine-dependent T-cell migration Blood, June 15, 2007; 109(12): 5122 - 5128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Abram and C. A. Lowell The Expanding Role for ITAM-Based Signaling Pathways in Immune Cells Sci. Signal., March 13, 2007; 2007(377): re2 - re2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. N. Kremer, A. Kumar, and K. E. Hedin Haplotype-Independent Costimulation of IL-10 Secretion by SDF-1/CXCL12 Proceeds via AP-1 Binding to the Human IL-10 Promoter J. Immunol., February 1, 2007; 178(3): 1581 - 1588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Richardson, C. Matthews, M. A. Catherwood, H. D. Alexander, B. S. Carey, J. Farrugia, A. Gardiner, S. Mould, D. Oscier, J. A. Copplestone, et al. ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL) Blood, May 1, 2006; 107(9): 3584 - 3592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Vianello, N. Papeta, T. Chen, P. Kraft, N. White, W. K. Hart, M. F. Kircher, E. Swart, S. Rhee, G. Palu, et al. Murine B16 Melanomas Expressing High Levels of the Chemokine Stromal-Derived Factor-1/CXCL12 Induce Tumor-Specific T Cell Chemorepulsion and Escape from Immune Control. J. Immunol., March 1, 2006; 176(5): 2902 - 2914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wu, D.-J. Li, M.-M. Yuan, Y. Zhu, and M.-Y. Wang The Expression of CXCR4/CXCL12 in First-Trimester Human Trophoblast Cells Biol Reprod, June 1, 2004; 70(6): 1877 - 1885. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
