Does MK5 reconcile classical and atypical MAP kinases?
MAP kinase-activated protein kinase 5 (MK5) was originally described as a protein kinase activated downstream of the p38 MAP kinase and is also named p38-regulated/activated protein kinase (PRAK). However, while MK5 is most similar in sequence to the two p38 regulated MAPKAP kinases MK2 and MK3, recent data has shown that in contrast to these enzymes MK5 is not activated in response to either cellular stress or pro-inflammatory cytokines. This lack of response to stimuli which cause robust activation of p38 MAP kinase in vivo is supported by data obtained using transgenic mice lacking MK5. Unlike animals lacking MK2 and MK3, MK5 null mice respond normally to endotoxic shock and display an unchanged pattern of cytokine expression in response to LPS. Clues as to the physiological function of MK5 have come from the recent observation that MK5 is uniquely regulated and activated following complex formation with the atypical MAP kinases ERK3 and ERK4. Thus, it is possible that MK5 is unique amongst the MAPKAP kinases in being regulated downstream of signaling pathways other than the classical MAP kinases p38 and ERK1/2.
Perander
Maria
M
Department of Pharmacology, Institute of Medical Biology, University of Tromso, N-9037 Tromso, Norway.
Keyse
Stephen M
SM
Seternes
Ole-Morten
OM
D017398:Alternative Splicing; D000818:Animals; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D048053:Mitogen-Activated Protein Kinase 6 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; C111049:MAP-kinase-activated kinase 5; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048053:Mitogen-Activated Protein Kinase 6; D048051:p38 Mitogen-Activated Protein Kinases