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

Lindholm, Cecilia KUppsala universitet,Institutionen för medicinsk cellbiologi (författare)

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.

Gylfe, Erik,1947-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)erikgylf (författare)
Zhang, Weigu (författare)
Samelson, Lawrence E (författare)
Welsh, MichaelUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)michwels (författare)
Uppsala universitetInstitutionen för medicinsk cellbiologi (creator_code:org_t)

Ingår i:Journal of Biological Chemistry: Elsevier BV274:39, s. 28050-280570021-92581083-351X

Av författaren/redakt...: Lindholm, Cecili ...; Gylfe, Erik, 194 ...; Zhang, Weigu; Samelson, Lawren ...; Welsh, Michael

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