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lüll Canonical and alternative MAPK signaling Pimienta G; Pascual JCell Cycle 2007[Nov]; 6 (21): 2628-32The 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.|Animals[MESH]|Enzyme Activation/physiology[MESH]|Humans[MESH]|MAP Kinase Signaling System/*physiology[MESH]|Mitogen-Activated Protein Kinases/*chemistry/metabolism/*physiology[MESH]|Substrate Specificity/physiology[MESH] |