A motif in the V3 domain of the kinase PKC-Î̧ determines its localization in the immunological synapse and functions in T cells via association with CD28

Kok Fai Kong, Tadashi Yokosuka, Ann J. Canonigo-Balancio, Noah Isakov, Takashi Saito, Amnon Altman

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Protein kinase C-θ (PKC-θ) translocates to the center of the immunological synapse, but the underlying mechanism and its importance in T cell activation are unknown. Here we found that the V3 domain of PKC-θ was necessary and sufficient for localization to the immunological synapse mediated by association with the coreceptor CD28 and dependent on the kinase Lck. We identified a conserved proline-rich motif in V3 required for association with CD28 and immunological synapse localization. We found association with CD28 to be essential for PKC-θ-mediated downstream signaling and the differentiation of T helper type 2 cells (T H2 cells) and interleukin 17-producing helper T cells (T H17 cells) but not of T helper type 1 cells (T H1 cells). Ectopic expression of V3 sequestered PKC-θ from the immunological synapse and interfered with its functions. Our results identify a unique mode of CD28 signaling, establish a molecular basis for the immunological synapse localization of PKC-θ and indicate V3-based 'decoys' may be therapeutic modalities for T cell-mediated inflammatory diseases.

Original languageEnglish
Pages (from-to)1105-1112
Number of pages8
JournalNature Immunology
Volume12
Issue number11
DOIs
StatePublished - 1 Nov 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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