Mitogen-activated protein kinase p38 and MK2, MK3 and MK5: ménage à trois or ménage à quatre?
The mitogen-activated protein kinase (MAPK) signalling pathways play pivotal roles in cellular processes such as proliferation, apoptosis, gene regulation, differentiation, and cell motility. The typical mammalian MAPK pathways ERK1/2, JNK, p38(MAPK), and ERK5 operate through a concatenation of three successive phosphorylation events mediated by a MAPK kinase kinase, a MAPK kinase, and a MAPK. MAPKs phosphorylate substrates with distinct functions, including other protein kinases referred to as MAPK-activated protein kinases. One family of related MAPK-activated protein kinases includes MK2, MK3, and MK5. While it is generally accepted that MK2 and MK3 are bona fide substrates for p38(MAPK), the genuineness of MK5 as a p38(MAPK) substrate is disputed. This review summarizes the findings pro and contra an authentic p38(MAPK)-MK5 relationship, discusses possible explanations for these discrepancies, and proposes experiments that may help to unequivocally clarify whether MK5 is indeed a substrate for p38(MAPK).
University of Tromsø, Faculty of Health Sciences, Institute of Medical Biology, N-9037 Tromsø, Norway.
Alexey
A
Shiryaev
Ugo
U
Moens
D000595:Amino Acid Sequence; D000818:Animals; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000099190:MAP-Kinase-Activated Kinase 2
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C111049:MAP-kinase-activated kinase 5; C098416:MAP-kinase-activated kinase 3