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- Title
Critical role of novel Thr-219 autophosphorylation for the cellular function of PKCθ in T lymphocytes.
- Authors
Thuille, Nikolaus; Heit, Isabelle; Fresser, Friedrich; Krumböck, Nina; Bauer, Birgit; Leuthaeusser, Sabine; Dammeier, Sascha; Graham, Caroline; Copeland, Terry D.; Shaw, Steve; Baier, Gottfried
- Abstract
Phosphopeptide mapping identified a major autophosphorylation site, phospho (p)Thr-219, between the tandem C1 domains of the regulatory fragment in protein kinase C (PKC)θ. Confirmation of this identification was derived using (p)Thr-219 antisera that reacted with endogenous PKCθ in primary CD3+ T cells after stimulation with phorbol ester, anti-CD3 or vanadate. The T219A mutation abrogated the capacity of PKCθ to mediate NF-κB, NF-AT and interleukin-2 promoter transactivation, and reduced PKCθ's ability in Jurkat T cells to phosphorylate endogenous cellular substrates. In particular, the T219A mutation impaired crosstalk of PKCθ with Akt/PKBα in NF-κB activation. Yet, this novel (p)Thr-219 site did not affect catalytic activity or second-messenger lipid-binding activity in vitro. Instead, the T219A mutation prevented proper recruitment of PKCθ in activated T cells. The PKCθT219A mutant defects were largely rescued by addition of a myristoylation signal to force its proper membrane localization. We conclude that autophosphorylation of PKCθ at Thr-219 plays an important role in the correct targeting and cellular function of PKCθ upon antigen receptor ligation.
- Subjects
PROTEIN kinase C; PHOSPHORYLATION; T cells; IMMUNE serums; PHORBOL esters; GENETIC mutation
- Publication
EMBO Journal, 2005, Vol 24, Issue 22, p3869
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7600856