Involvement of SHP-1 tyrosine phosphatase in TCR-mediated signaling pathways in lipid rafts.
To elucidate the process of TCR-mediated signaling pathways in lipid rafts, we constructed a chimeric molecule that localizes activated SHP-1 to rafts. Raft targeting of activated SHP-1 in Jurkat-derived transfectants completely inhibited the expression of CD69 and transcriptional factors after TCR cross-linking. Whereas the inducible tyrosine phosphorylation of TCR zeta and ZAP-70 and the kinase activity of Lck were intact, phosphorylated LAT was rapidly dephosphorylated by raft targeting of activated SHP-1, leading to defects in LAT activation and subsequent downstream signaling events. Intriguingly, recruitment of endogenous SHP-1 to rafts and its association with LAT were dramatically increased after TCR engagement, suggesting that SHP-1 is involved in raft-mediated T cell activation.
Kosugi
A
A
School of Allied Health Sciences, Faculty of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. kosugi@sahs.med.osaka-u.ac.jp
Sakakura
J
J
Yasuda
K
K
Ogata
M
M
Hamaoka
T
T
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D010168:Palmitates / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C110810:LAT protein, human; D008565:Membrane Proteins; D010168:Palmitates; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C054979:antigen T cell receptor, zeta chain; D014443:Tyrosine; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D002118:Calcium