Cutting edge: a novel function for the SLAP-130/FYB adapter protein in beta 1 integrin signaling and T lymphocyte migration.
The role of integrin-mediated signaling events in T cell function remains incompletely characterized. We report here that alpha4beta1 integrin stimulation of H9 T cells and normal human T cell blasts results in rapid and transient tyrosine phosphorylation of the adapter protein, SH2 domain-containing 76-kDa protein (SLP-76)-associated phosphoprotein of 130 kDa (SLAP-130)/FYB at levels comparable to those observed following TCR stimulation. Stimulation of T cells via the alpha4beta1 integrin enhances the association of tyrosine phosphorylated SLAP-130/FYB with the SH2 domain of the src tyrosine kinase p59fyn. Activation of normal T cells, but not H9 T cells, via alpha4beta1 leads to tyrosine phosphorylation of SLP-76 as well as SLAP-130/FYB. Overexpression of SLAP-130/FYB in normal T cells enhances T cell migration through fibronectin-coated filters in response to the chemokine stromal cell-derived factor (SDF)-1alpha. These results identify SLAP-130/FYB as a new tyrosine phosphorylated substrate in beta1 integrin signaling and suggest a novel function for SLAP-130/FYB in regulating T lymphocyte motility.
Hunter
A J
AJ
Department of Laboratory Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Ottoson
N
N
Boerth
N
N
Koretzky
G A
GA
Shimizu
Y
Y
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C106957:FYB1 protein, human; C491468:Fyb protein, mouse; D039041:Integrin alpha4beta1; D016023:Integrins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D016201:Receptors, Lymphocyte Homing; C490635:SLA protein, human; C092947:SLP-76 signal Transducing adaptor proteins; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)