PKCtheta cooperates with atypical PKCzeta and PKCiota in NF-kappaB transactivation of T lymphocytes

Mol Immunol. 2008 Jan;45(1):117-26. doi: 10.1016/j.molimm.2007.05.003. Epub 2007 Jun 22.


Using yeast two-hybrid, we isolated atypical PKCzeta as a PKCtheta-interacting kinase and demonstrated that it selectively interacted with, and was phosphorylated by, PKCtheta. Importantly, however, both atypical PKCzeta and PKCiota were functionally required in TCR/CD28-mediated activation of NF-kappaB downstream of PKCtheta in Jurkat T cells albeit, activation responses of PKCzeta-deficient CD3+ T cells were comparable with wildtype controls. This normal activation thresholds of PKCzeta-/- T cells suggested that PKCiota, the closest structural relative, might play a compensatory role in TCR/CD28-induced signalling. Consistently, both PKCzeta and PKCiota resided in the plasma membrane lipid raft microdomains of Jurkat as well as primary mouse CD3+ T cells. Thus, PKCtheta, the established constituent of the immunological synapse, physically and functionally interacted with PKCzeta and PKCiota. Together, these data demonstrate that atypical PKCzeta/iota isotypes serve as direct downstream targets of PKCtheta in the signalling pathway leading to NF-kappaB activation in T lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex
  • Catalytic Domain
  • Cell Proliferation
  • Genes, Dominant
  • Humans
  • Interleukin-2 / metabolism
  • Isoenzymes / metabolism
  • Jurkat Cells
  • Membrane Microdomains / enzymology
  • Mice
  • NF-kappa B / metabolism*
  • Protein Binding
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Protein Transport
  • Rats
  • Substrate Specificity
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / metabolism
  • Transcriptional Activation / genetics*
  • Transfection


  • CD3 Complex
  • Interleukin-2
  • Isoenzymes
  • NF-kappa B
  • protein kinase C zeta
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta
  • protein kinase C lambda