Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-κB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain

Stephan Witte, Martin Villalba, Kun Bi, Yuhong Liu, Noah Isakov, Amnon Altman

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

Abstract

Protein kinase C-θ (PKCθ) is a Ca2+-independent PKC isoform that is selectively expressed in T lymphocytes (and muscle), and is thought to play an important role in T cell receptor-induced activation. To gain a better understanding of the function and regulation of PKCθ, we have employed the yeast two-hybrid system to identify PKCθ-interacting proteins. We report the isolation and characterization of a cDNA encoding a novel 335-amino acid (37.5-kDa) PKCθ-interacting protein termed PICOT (for PKC-interacting cousin of thioredoxin). PICOT is expressed in various tissues, including in T cells, where it colocalizes with PKCθ. PICOT displays an N-terminal thioredoxin homology domain, which is required for the interaction with PKC. Comparison of the unique C-terminal region of PICOT with expressed sequence tag data bases revealed two tandem repeats of a novel domain that is highly conserved from plants to mammals. Transient overexpression of full-length PICOT (but not its N- or C-terminal fragments) in T cells inhibited the activation of c- Jun N-terminal kinase (but not extracellular signal-regulated kinase), and the transcription factors AP-1 or NF-κB. These findings suggest that PICOT and its evolutionary conserved homologues may interact with PKC-related kinases in multiple organisms and, second, that it plays a role in regulating the function of the thioredoxin system.

Original languageEnglish
Pages (from-to)1902-1909
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number3
DOIs
StatePublished - 21 Jan 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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