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.
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.
Okabe
Seiichi
S
Department of Microbiology/Immunology and Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Tauchi
Tetsuzo
T
Ohyashiki
Kazuma
K
Broxmeyer
Hal E
HE
D000293:Adolescent; D000328:Adult; D000368:Aged; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D002633:Chemotaxis; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D019061:src-Family Kinases / Q000378:metabolism*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D050721:Proto-Oncogene Proteins c-cbl; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens; C067419:CBL protein, human