TCR-induced, PKC-θ-mediated NF-κB activation is regulated by a caspase-8-caspase-9-caspase-3 cascade

Biochem Biophys Res Commun. 2014 Jul 18;450(1):526-31. doi: 10.1016/j.bbrc.2014.06.010. Epub 2014 Jun 9.

Abstract

It has been documented that caspase-8, a central player in apoptosis, is also crucial for TCR-mediated NF-κB activation. However, whether other caspases are also involved this process is unknown. In this report, we showed that in addition to caspase-8, caspase-9 is required for TCR-mediated NF-κB activation. Caspase-9 induces activation of PKC-θ, phosphorylation of Bcl10 and NF-κB activation in a caspase-3-dependent manner, but it appears that Bcl10 phosphorylation is uncoupled from NF-κB activation. Furthermore, caspase-8 lies upstream of caspase-9 during T cell activation. Therefore, TCR ligation elicits a caspase cascade involving caspase-8, caspase-9 and caspase-3 which initiates PKC-θ-dependent pathway leading to NF-κB activation and PKC-θ-independent Bcl10 phosphorylation which limits NF-kB activity.

Keywords: Caspase-9; NF-κB; T cell activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspases / metabolism*
  • Cells, Cultured
  • Humans
  • Isoenzymes / metabolism*
  • Jurkat Cells
  • Lymphocyte Activation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Multienzyme Complexes / metabolism
  • NF-kappa B / metabolism*
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes

Substances

  • Isoenzymes
  • Multienzyme Complexes
  • NF-kappa B
  • Receptors, Antigen, T-Cell
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta
  • Caspases