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

Seiichi Okabe, Tetsuzo Tauchi, Kazuma Ohyashiki, Hal E. Broxmeyer

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Stromal-cell-derived factor-1α (SDF-1α/CXCL12) is a potent chemoattractant for T cells. We report that Cbl family members, Cbl and Cbl-b, are tyrosine-phosphorylated after SDF-1α/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-γ and Fyb after SDF-1α/CXCL12 stimulation, implicating association of these proteins in SDF-1α/CXCL12 actions. SDF-1α/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-1α/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-1α/CXCL12- induced cell migration of Jurkat T cells.

Original languageEnglish (US)
Pages (from-to)308-314
Number of pages7
JournalBlood Cells, Molecules, and Diseases
Volume36
Issue number2
DOIs
StatePublished - Mar 1 2006

Keywords

  • Cbl
  • CD45
  • Chemotaxis
  • Jurkat cells
  • Lck
  • SDF-1/CXCL12
  • Signal transduction
  • Src kinases
  • T lymphocytes

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology

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