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 Mol Dis. Mar-Apr 2006;36(2):308-14. doi: 10.1016/j.bcmd.2005.12.035. Epub 2006 Feb 28.

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-1alpha/CXCL12-induced cell migration of Jurkat T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chemokine CXCL12
  • Chemokines, CXC / physiology*
  • Chemotaxis*
  • Female
  • Humans
  • Jurkat Cells
  • Leukocyte Common Antigens / metabolism
  • Leukocyte Common Antigens / physiology*
  • Male
  • Middle Aged
  • Phosphorylation
  • Proto-Oncogene Proteins c-cbl / metabolism
  • Proto-Oncogene Proteins c-cbl / physiology*
  • Signal Transduction*
  • T-Lymphocytes / cytology*
  • src-Family Kinases / metabolism*

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Proto-Oncogene Proteins c-cbl
  • src-Family Kinases
  • Leukocyte Common Antigens
  • CBL protein, human