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 Broxmeyer

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22 Citations (Scopus)

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

Fingerprint

Chemokine CXCL12
src-Family Kinases
Chemotaxis
T-Lymphocytes
Cell Line
Tyrosine
Jurkat Cells
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Phosphorylation
Chemotactic Factors
Phosphoric Monoester Hydrolases
Small Interfering RNA
Cell Movement
Proteins

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

Cite this

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title = "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",
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.",
keywords = "Cbl, CD45, Chemotaxis, Jurkat cells, Lck, SDF-1/CXCL12, Signal transduction, Src kinases, T lymphocytes",
author = "Seiichi Okabe and Tetsuzo Tauchi and Kazuma Ohyashiki and Hal Broxmeyer",
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T1 - 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

AU - Okabe, Seiichi

AU - Tauchi, Tetsuzo

AU - Ohyashiki, Kazuma

AU - Broxmeyer, Hal

PY - 2006/3

Y1 - 2006/3

N2 - 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.

AB - 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.

KW - Cbl

KW - CD45

KW - Chemotaxis

KW - Jurkat cells

KW - Lck

KW - SDF-1/CXCL12

KW - Signal transduction

KW - Src kinases

KW - T lymphocytes

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U2 - 10.1016/j.bcmd.2005.12.035

DO - 10.1016/j.bcmd.2005.12.035

M3 - Article

VL - 36

SP - 308

EP - 314

JO - Blood Cells, Molecules, and Diseases

JF - Blood Cells, Molecules, and Diseases

SN - 1079-9796

IS - 2

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