Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the Interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells
1999 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 274, no 39, 28050-28057 p.Article in journal (Refereed) Published
Stimulation of the T cell antigen receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins. We have recently investigated the role of the adaptor protein Shb in the early events of T cell signaling and observed that Shb associates with Grb2, linker for activation of T cells (LAT) and the TCR zeta-chain in Jurkat cells. We now report that Shb also associates with phospholipase C-gamma1 (PLC-gamma1) in these cells. Overexpression of Src homology 2 domain defective Shb caused diminished phosphorylation of LAT and consequently the activation of mitogen-activated protein kinases was decreased upon TCR stimulation. In addition, the Shb mutant also blocked phosphorylation of PLC-gamma1 and the increase in cytoplasmic Ca(2+) following TCR stimulation. Nuclear factor for activation of T cells is a major target for Ras and calcium signaling pathways in T cells following TCR stimulation, and the overexpression of the mutant Shb prevented TCR-dependent activation of the nuclear factor for activation of T cells. Consequently, endogenous interleukin-2 production was decreased under these conditions. The results indicate a role for Shb as a link between the TCR and downstream signaling events involving LAT and PLC-gamma1 and resulting in the activation of transcription of the interleukin-2 gene.
Place, publisher, year, edition, pages
1999. Vol. 274, no 39, 28050-28057 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-89705DOI: 10.1074/jbc.274.39.28050PubMedID: 10488157OAI: oai:DiVA.org:uu-89705DiVA: diva2:161401