SKAP55 Recruits to Lipid Rafts and Positively Mediates the MAPK Pathway upon T Cell ReceptorâActivation
T cell receptor (TCR) engagement triggers a series of events including protein tyrosine kinase activation, tyrosine phosphorylation of adapter proteins, and multiple protein-protein interactions. We observed that adapter protein SKAP55, the Src kinase-associated phosphoprotein, formed homodimers thr...
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Published in | The Journal of biological chemistry Vol. 277; no. 43; p. 40420 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
25.10.2002
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Online Access | Get full text |
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Summary: | T cell receptor (TCR) engagement triggers a series of events including protein tyrosine kinase activation, tyrosine phosphorylation
of adapter proteins, and multiple protein-protein interactions. We observed that adapter protein SKAP55, the Src kinase-associated
phosphoprotein, formed homodimers through its SH3 domain and SK region. SKAP55 as a substrate interacted with Fyn kinase in vivo . In Jurkat cells, interaction between SKAP55 and Fyn kinase depended on TCR activation. Stable overexpression of SKAP55 in
Jurkat cells caused mitogen-activated protein kinase activation following TCR engagement. Anti-CD3 stimulation also promoted
the interaction of SKAP55 with Grb-2 in T cells. Mutational analysis revealed that tyrosine 271 in SKAP55 played a pivotal
role for interaction with both Fyn kinase and adapter protein Grb-2, indicating that the Fyn-phosphorylated SKAP55 transiently
associates with adapter Grb-2 to mediate mitogen-activated protein kinase activation. Intriguingly, T cell receptor engagement
dramatically induced the translocation of endogenous SKAP55 to lipid rafts where SKAP55 was found to interact with Fyn kinase,
suggesting that the positive function of SKAP55 via its association with Fyn and other signaling components may have been
involved in raft-mediated T cell activation. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M206023200 |