Src kinase, but not the src kinase family member p56lck, mediates stromal cell-derived factor 1alpha/CXCL12-induced chemotaxis of a T cell line.
Stromal cell-derived factor 1 (SDF-1/CXCL12) is believed to mediate migration of leukocytes. To explore potential mechanisms, we evaluated the signal transduction pathways activated by SDF-1 in the Jurkat T cell line. Src kinase was phosphorylated and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) activated in a time-related fashion after SDF-1 stimulation. Chemotaxis of Jurkat cells was partially blocked by pretreatment with the src kinase inhibitor PP2 in a dose-dependent manner. Wiskott-Aldrich Syndrome Protein (WASP) regulates actin polymerization and cytoskeletal organization in T cells. We found WASP complexed to activated src after SDF-1 stimulation, suggesting a possible interacting role for src kinase and WASP in mediating SDF-1 action. J.CaM1.6 cells, which have lost expression of the src kinase p56(lck) (lck), responded to chemotaxis induced by SDF-1 as well as the parental Jurkat cells. Because J.CaM1.6 cells respond as well as the parental cells to SDF-1 in terms of ERK activation and tyrosine phosphorylation of WASP after SDF-1 stimulation, it appears that src kinase, but not the src kinase family member lck, mediates chemotaxis of Jurkat cells in response to SDF-1 induction and that src kinase may link with WASP in this effect.
Okabe
Seiichi
S
Department of Microbiology/Immunology and Medicine, and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202-5254, USA.
Fukuda
Seiji
S
Broxmeyer
Hal E
HE
D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D051316:Wiskott-Aldrich Syndrome Protein; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases