Stromal-cell-derived factor-1/CXCL12-induced chemotaxis of a T cell line involves intracellular signaling through Cbl and Cbl-b and their regulation by Src kinases and CD45

Blood Cells, Molecules & Diseases
Seiichi OkabeHal E Broxmeyer

Abstract

Stromal-cell-derived factor-1alpha (SDF-1alpha/CXCL12) is a potent chemoattractant for T cells. We report that Cbl family members, Cbl and Cbl-b, are tyrosine-phosphorylated after SDF-1alpha/CXCL12 stimulation of Jurkat T cells. Enhanced phosphorylation of Cbl and Cbl-b was regulated by src family kinases, and perhaps Fyn. Activated Cbl and Cbl-b interacted with Crk-L, Zap-70, Nck, PLC-gamma and Fyb after SDF-1alpha/CXCL12 stimulation, implicating association of these proteins in SDF-1alpha/CXCL12 actions. SDF-1alpha/CXCL12 did not induce tyrosine phosphorylation of Cbl or Cbl-b in Lck-deficient T cell line J.CaM1.6 or CD45-deficient T cell line J45.01. Thus, Lck Src kinase and tyrosine phosphatase CD45 are likely involved in regulating activation of Cbl family members. A functional role for Cbl and Cbl-b in migration was demonstrated by the decrease in SDF-1/CXCL12-induced migration in a T cell line in which transfected small interfering RNA for Cbl and Cbl-b decreased expression of Cbl and Cbl-b, but not MAPK activity. SDF-1alpha/CXCL12-induced chemotaxis was greatly reduced in the CD45-deficient T cell line. Our results implicate CD45, Cbl, Cbl-b, src kinases and potentially other associated proteins as mediators of SDF-1alp...Continue Reading

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Citations

Sep 29, 2011·Calcified Tissue International·Tracy BrennanArchana Sanjay
Sep 17, 2008·Immunologic Research·Rebecca G Baker, Gary A Koretzky
Nov 29, 2007·Current Opinion in Hematology·Hal E Broxmeyer
Dec 31, 2009·PLoS Pathogens·Yuntao Wu, Alyson Yoder
Dec 7, 2007·Immunology Letters·Laura Patrussi, Cosima T Baldari
Oct 7, 2015·Stem Cell Research & Therapy·Michael J RuttenKenton W Gregory
Jun 29, 2013·Biochimica Et Biophysica Acta·Wasim Abbas, Georges Herbein
Oct 29, 2009·Cellular Signalling·A E Saunders, P Johnson
Apr 3, 2009·Biochemical and Biophysical Research Communications·Seiichi OkabeKazuma Ohyashiki
Sep 23, 2014·International Immunology·Tatsuki R KataokaHironori Haga
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Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Seiichi OkabeKazuma Ohyashiki
Dec 12, 2020·Clinical and Experimental Immunology·D JafariA Esmaeilzadeh

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