Protein kinase Ctheta, a selective upstream regulator of JNK/SAPK and IL-2 promoter activation in Jurkat T cells

Eur J Immunol. 1999 Jan;29(1):132-42. doi: 10.1002/(SICI)1521-4141(199901)29:01<132::AID-IMMU132>3.0.CO;2-7.

Abstract

The predominant expression of protein kinase C (PKC) theta in T cells (J. Biol. Chem. 1993. 268: 4997-5004), its isoenzyme-specific ability to stimulate AP-1 transcriptional activity (Mol. Cell. Biol. 1996. 16: 1842-1850) and the recent discovery of its selective and antigen-dependent colocalization with the contact region between T cells and antigen-presenting cells (Nature 1997. 385: 83-89) suggest that, among the PKC family members, PKCtheta plays a specialized role in T cell activation. By investigating the downstream effectors of PKCtheta we now demonstrate a direct and isoenzyme-specific contribution of PKCtheta to c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) but not extracellular regulated kinase (ERK) activation. Expression of a constitutively active (CA) form of PKCtheta (but not CA-PKCalpha, epsilon and lambda/iota) resulted in strong activation of JNK/SAPK and expression of a dominant-negative form of PKCtheta interfered with the endogenous activation signal for JNK/SAPK. Importantly, Ca2+ ionophore and CA-PKCtheta (but not CA-PKCalpha, epsilon and lambda/iota) caused synergistic activation of the IL-2 promoter. Together, these data establish that PKCtheta is required for activation of JNK/SAPK signaling leading to IL-2 promoter transcription in T lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisomycin / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Enzyme Activation / drug effects
  • Fetal Proteins / metabolism
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Interleukin-2 / genetics*
  • Ionomycin / pharmacology
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Jurkat Cells
  • Lymphocyte Activation
  • MAP Kinase Kinase Kinase 1*
  • Mitogen-Activated Protein Kinases / metabolism
  • Promoter Regions, Genetic*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphA4
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection

Substances

  • Fetal Proteins
  • Interleukin-2
  • Isoenzymes
  • Ionomycin
  • Anisomycin
  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphA4
  • Protein-Serine-Threonine Kinases
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • Tetradecanoylphorbol Acetate