Relations between the mitogen-activated protein kinase and the cAMP-dependent protein kinase pathways: comradeship and hostility

Cell Signal. 2008 Sep;20(9):1592-607. doi: 10.1016/j.cellsig.2008.02.022. Epub 2008 Mar 14.


Inter- and intracellular communications and responses to environmental changes are pivotal for the orchestrated and harmonious operation of multi-cellular organisms. These well-tuned functions in living organisms are mediated by the action of signal transduction pathways, which are responsible for receiving a signal, transmitting and amplifying it, and eliciting the appropriate cellular responses. Mammalian cells posses numerous signal transduction pathways that, rather than acting in solitude, interconnect with each other, a phenomenon referred to as cross-talk. This allows cells to regulate the distribution, duration, intensity and specificity of the response. The cAMP/cAMP-dependent protein kinase (PKA) pathway and the mitogen-activated protein kinase (MAPK) cascades modulate common processes in the cell and multiple levels of cross-talk between these signalling pathways have been described. The first- and best-characterized interconnections are the PKA-dependent inhibition of the MAPKs ERK1/2 mediated by RAF-1, and PKA-induced activation of ERK1/2 interceded through B-RAF. Recently, novel interactions between components of these pathways and new mechanisms for cross-talk have been elucidated. This review discusses both known and novel interactions between compounds of the cAMP/PKA and MAPKs signalling pathways in mammalian cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Substrate Specificity


  • Intracellular Signaling Peptides and Proteins
  • MAP-kinase-activated kinase 5
  • Protein-Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases, 90-kDa
  • Cyclic AMP-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases