Canonical and alternative MAPK signaling.
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.
Pimienta
Genaro
G
Inflammation and Infectious Diseases Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Pascual
Jaime
J
D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D013379:Substrate Specificity / Q000502:physiology
D020928:Mitogen-Activated Protein Kinases