TAILIEUCHUNG - Báo cáo Y học: Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells

This study addresses the interactions between the adaptor protein Shb and components involved in T cell signalling, including SLP-76, Gads, Vav and ZAP70. We show that both SLP-76 and ZAP70 co-immunoprecipitate with Shb in Jurkat T cells and that Shb and Vav co-immunoprecipitate when cotransfected in COS cells. We also demonstrate, utilizing fusion protein constructs, that SLP-76, Gads and Vav associate independently of each other to different domains or regions, of Shb. | Eur. J. Biochem. 269 3279-3288 2002 FEBS 2002 doi Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells Cecilia K. Lindholm1 Maria L. Henriksson2 Bengt Hallberg2 and Michael Welsh1 1 Department of Medical Cell Biology Biomedicum Uppsala University Sweden department of Medical Biosciences Pathology Umea University Sweden This study addresses the interactions between the adaptor protein Shb and components involved in T cell signalling including SLP-76 Gads Vav and ZAP70. We show that both SLP-76 and ZAP70 co-immunoprecipitate with Shb in Jurkat T cells and that Shb and Vav co-immunoprecipitate when cotransfected in COS cells. We also demonstrate utilizing fusion protein constructs that SLP-76 Gads and Vav associate independently of each other to different domains or regions of Shb. Overexpression of an SH2 domain-defective Shb causes diminished phosphorylation of SLP-76 and Vav and consequently decreased activation of c-Jun kinase upon T cell receptor TCR stimulation. Shb was also found to localize to glycolipid-enriched membrane microdomains GEMs also called lipid rafts after TCR stimulation. Our results indicate that upon TCR stimulation Shb is targeted to these lipid rafts where Shb aids in recruiting the SLP-76-Gads-Vav complex to the T cell receptor f-chain and ZAP70. Keywords Shb Vav sI r - fv T cell receptor lipid raftt. The early events in T cell signalling involve the activation of Lck which subsequently phosphorylates the TCR f-chain and the e-chain of the CD3 complex on ITAM motifs immunoreceptor tyrosine-based activation motifs . This recruits the kinases ZAP70 or Syk that consequently induces tyrosine phosphorylation of several intracellular substrates for example phospholipase C-y1 PLC-71 . LAT 1 Vav and SLP-76 2 . Functional interactions between these effector molecules are believed to be necessary for T cell maturation proliferation and differentiation. One aspect of T cell receptor TCR activation relates to

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