Format

Send to

Choose Destination
Cell Commun Signal. 2015 Mar 31;13:22. doi: 10.1186/s12964-015-0100-3.

Novel protein kinase C θ: coronin 1A complex in T lymphocytes.

Author information

1
Department for Pharmacology and Genetics, Division of Translational Cell Genetics, Medical University Innsbruck, Peter Mayr Str. 1a, A-6020, Innsbruck, Austria. kerstin.siegmund@i-med.ac.at.
2
Department for Pharmacology and Genetics, Division of Translational Cell Genetics, Medical University Innsbruck, Peter Mayr Str. 1a, A-6020, Innsbruck, Austria. nikolaus.thuille@i-med.ac.at.
3
Department for Pharmacology and Genetics, Division of Translational Cell Genetics, Medical University Innsbruck, Peter Mayr Str. 1a, A-6020, Innsbruck, Austria. nina.krumboeck@i-med.ac.at.
4
Department for Pharmacology and Genetics, Division of Translational Cell Genetics, Medical University Innsbruck, Peter Mayr Str. 1a, A-6020, Innsbruck, Austria. friedrich.fresser@i-med.ac.at.
5
Department for Pharmacology and Genetics, Division of Translational Cell Genetics, Medical University Innsbruck, Peter Mayr Str. 1a, A-6020, Innsbruck, Austria. gottfried.baier@i-med.ac.at.

Abstract

BACKGROUND:

Protein kinase C-θ (PKCθ) plays an important role in signal transduction down-stream of the T cell receptor and T cells deficient of PKCθ show impaired NF-κB as well as NFAT/AP-1 activation resulting in strongly decreased IL-2 expression and proliferation. However, it is not yet entirely clear, how the function of PKCθ - upon T cell activation - is regulated on a molecular level.

FINDINGS:

Employing a yeast two-hybrid screen and co-immunoprecipitation analyses, we here identify coronin 1A (Coro1A) as a novel PKCθ-interacting protein. We show that the NH2-terminal WD40 domains of Coro1A and the C2-like domain of PKCθ are sufficient for the interaction. Furthermore, we confirm a physical interaction by GST-Coro1A mediated pull-down of endogenous PKCθ protein. Functionally, wild-type but not Coro1A lacking its actin-binding domain negatively interferes with PKCθ-dependent NF-κB, Cyclin D1 and IL-2 transactivation when analysed with luciferase promoter activation assays in Jurkat T cells. This could be phenocopied by pharmacological inhibitors of actin polymerization and PKC, respectively. Mechanistically, Coro1A overexpression attenuates both lipid raft and plasma membrane recruitment of PKCθ in CD3/CD28-activated T cells. Using primary CD3(+) T cells, we observed that (opposite to PKCθ) Coro1A does not localize preferentially to the immunological synapse. In addition, we show that CD3(+) T cells isolated from Coro1A-deficient mice show impaired IKK/NF-κB transactivation.

CONCLUSIONS:

Together, these findings both in Jurkat T cells as well as in primary T cells indicate a regulatory role of Coro1A on PKCθ recruitment and function downstream of the TCR leading to NF-κB transactivation.

PMID:
25889880
PMCID:
PMC4390099
DOI:
10.1186/s12964-015-0100-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center