The many paths to p38 mitogen-activated protein kinase activation in the immune system

Nat Rev Immunol. 2006 Jul;6(7):532-40. doi: 10.1038/nri1865.


Signals emanating from many cell-surface receptors and environmental cues converge on mitogen-activated protein kinases (MAPKs), which in turn phosphorylate and activate various transcription factors and other molecular effectors. Members of the p38 MAPK family, which respond to pro-inflammatory cytokines and cellular stresses, are typically activated by serial phosphorylation and activation of upstream kinases (the MAPK cascade). In this Review, I highlight the recent studies that indicate that p38-subfamily members can also be activated by non-canonical mechanisms, at least one of which seems to have an important role in antigen-receptor-activated T cells. These alternative pathways might have particular relevance for cells that participate in immune and inflammatory responses.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Enzyme Activation / immunology*
  • Humans
  • Immune System / enzymology*
  • Lymphocyte Activation / immunology
  • Models, Immunological*
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology
  • p38 Mitogen-Activated Protein Kinases / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • p38 Mitogen-Activated Protein Kinases