Positive feedback regulation of PLC gamma 1/Ca2+ signaling by PKC theta in restimulated T cells via a Tec kinase-dependent pathway

Abstract : PKCtheta plays an essential role in activation of mature T cells. Here, we report that the TCR/CD28-induced tyrosine phosphorylation and activation of PLCgamma1 was significantly impaired in PKCtheta(-/-) primary, restimulated T cells. Consistent with this finding, receptor-induced Ca2+ mobilization, NF-AT DNA-binding activity and the membrane translocation of PKCalpha, a PLCgamma1-dependent conventional PKC, were also markedly reduced in the same cells. Moreover, a dominant-negative PLCgamma1 mutant blocked the PKCtheta-induced activation of an AP-1 reporter gene in Jurkat and primary cells. Regulation of PLCgamma1 signaling by PKCtheta required the tyrosine kinase Tec since a dominant-negative Tec mutant blocked PKCtheta-induced AP-1 (but not NF-kappaB) activation. In addition, wild-type Tec, but not Itk or Rlk, potently activated AP-1. Furthermore, Tec was found to constitutively associate with PKCtheta, an interaction that like AP-1 activation required the pleckstrin-homology domain of Tec. These findings define a novel PKCtheta-initiated pathway that regulates Ca2+ signaling and AP-1 activation via Tec and PLCgamma1. Moreover, they identify Tec as a key point downstream of PKCtheta, where TCR- and PKCtheta-induced signaling pathways, leading to AP-1 versus NF-kappaB activation, diverge in T cells.
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Submitted on : Friday, August 2, 2019 - 2:21:59 PM
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A. Altman, S. Kaminski, V. Busuttil, N. Droin, J. R. Hu, et al.. Positive feedback regulation of PLC gamma 1/Ca2+ signaling by PKC theta in restimulated T cells via a Tec kinase-dependent pathway. European Journal of Immunology, Wiley-VCH Verlag, 2004, 34 (7), pp.2001--2011. ⟨hal-02262400⟩

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