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Cell Cycle. 2007 Nov 1;6(21):2628-32. Epub 2007 Aug 22.

Canonical and alternative MAPK signaling.

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  • 1Inflammation and Infectious Diseases Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.

Abstract

The archetype of MAPK cascade activation is somewhat challenged by the most recent discovery of unexpected phosphorylation patterns, alternative activation mechanisms and sub-cellular localization, in various members of this protein kinase family. In particular, activation by autophosphorylation pathways has now been described for the three best understood MAPK subgroups: ERK1/2; JNK1/2 and p38 alpha/beta. Also, a form of dosage compensation between homologs has been shown to occur in the case of ERK1/2 and JNK1/2. In this paper we summarize the MAPK activation pathway, with an emphasis on non-canonical examples. We use this information to propose a model for MAPK signal transduction that considers a cross-talk between MAPKs with different activation loop sequence motifs and unique C-terminal extensions. We highlight the occurrence of non-canonical substrate specificity during MAPK auto-activation, in strong connection with MAPK homo- and hetero-dimerization events.

PMID:
17957138
[PubMed - indexed for MEDLINE]
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