Co-stimulation-dependent Activation of a JNK-kinase in T Lymphocytes

Eur J Immunol. 1998 Aug;28(8):2320-30. doi: 10.1002/(SICI)1521-4141(199808)28:08<2320::AID-IMMU2320>3.0.CO;2-K.

Abstract

Previously we implicated c-Jun N-terminal kinase (JNK) as an element that is involved in signal integration during co-stimulation of T lymphocytes. This pathway has now been traced to an upper level, comprising MAPKK SEK1/MKK4/JNKK1 which, similarly to JNK, must receive input both from the TCR and CD28. A large portion of this input is probably integrated at the level of the Rho-family protein CDC42 which, here, activates SEK1 and JNK to the level reached by TCR and CD28 stimulation. We have identified another putative SEK/ JNK pathway regulator, PKCtheta, which in contrast to CDC42, activates SEK and JNK maximally only in conjunction with a calcium signal delivered through calcineurin. Signals originating at the TCR and CD28 may travel down the JNK pathway via PKCtheta, calcineurin, CDC42, MEKK1 and SEK1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcineurin / genetics
  • Calcineurin / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Cycle Proteins / metabolism
  • Enzyme Activation
  • GTP-Binding Proteins / metabolism
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • JNK Mitogen-Activated Protein Kinases
  • Jurkat Cells
  • Lymphocyte Activation
  • MAP Kinase Kinase 4*
  • Mice
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Mutation
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Protein Kinase C-theta
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology
  • Transfection
  • cdc42 GTP-Binding Protein

Substances

  • Cell Cycle Proteins
  • Isoenzymes
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • PRKCQ protein, human
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • MAP2K4 protein, human
  • Map2k4 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases
  • Calcineurin
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein