Activation of Wiskott-Aldrich syndrome protein and its association with other proteins by stromal cell-derived factor-1alpha is associated with cell migration in a T-lymphocyte line.
OBJECTIVES: Chemokines play a central role in lymphocyte trafficking and homing. The actin cytoskeleton is involved in cell morphological changes and motility. Wiskott-Aldrich syndrome (WAS) protein (WASP) has been implicated in regulation of cytoskeleton rearrangement. To evaluate mechanisms that might be involved in migration of T cells, we examined effects ... of stromal cell-derived factor (SDF)-1alpha on WASP and associated proteins. METHODS: Jurkat T cells were stimulated by SDF-1alpha and analyzed for chemotaxis and also by Western blot analysis for signal transduction. RESULTS: Jurkat T cells displayed chemotaxis to SDF-1alpha, which was inhibited by pretreatment of cells with either pertussis toxin, a Galphai protein inhibitor, wortmannin or Ly294002, phophatidylinositol 3-kinase inhibitors, or herbimycin, a protein tyrosine kinase inhibitor. WASP was tyrosine phosphorylated in response to SDF-1alpha stimulation in Jurkat T cells. Crk associated substrate (Cas), Nck, and focal adhesion kinase (FAK) were also phosphorylated after SDF-1alpha stimulation. Moreover, activated Nck interacted with Cas and WASP as determined by co-immunoprecipitation, and FAK also bound to Cas. CONCLUSIONS: These data suggest that WASP, Cas, Nck, and FAK may play a role in SDF-1alpha-induced migration of the T-cell line, Jurkat.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Actins, Adaptor Proteins, Signal Transducing, Biopolymers, Chemokine CXCL12, Chemokines, CXC, Chemotaxis, Crk-Associated Substrate Protein, Cytoskeleton, Enzyme Inhibitors, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Humans, Jurkat Cells, Macromolecular Substances, Neoplasm Proteins, Oncogene Proteins, Phosphoproteins, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Protein-Tyrosine Kinases, Proteins, Receptors, CXCR4, Recombinant Proteins, Retinoblastoma-Like Protein p130, Signal Transduction, T-Lymphocytes, Wiskott-Aldrich Syndrome Protein
1-Phosphatidylinositol 3-Kinase, Actins, Adaptor Proteins, Signal Transducing, Biopolymers, Chemokine CXCL12, Chemokines, CXC, Chemotaxis, Crk-Associated Substrate Protein, Cytoskeleton, Enzyme Inhibitors, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, Humans, Jurkat Cells, Macromolecular Substances, Neoplasm Proteins, Oncogene Proteins, Phosphoproteins, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Protein-Tyrosine Kinases, Proteins, Receptors, CXCR4, Recombinant Proteins, Retinoblastoma-Like Protein p130, Signal Transduction, T-Lymphocytes, Wiskott-Aldrich Syndrome Protein
Exp. Hematol.
Date: Jul. 01, 2002
PubMed ID: 12135674
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