ERK5: structure, regulation and function.
Extracellular signal-regulated kinase 5 (ERK5), also termed big mitogen-activated protein kinase-1 (BMK1), is the most recently identified member of the mitogen-activated protein kinase (MAPK) family and consists of an amino-terminal kinase domain, with a relatively large carboxy-terminal of unique structure and function that makes it distinct from other MAPK members. It is ubiquitously expressed in numerous tissues and is activated by a variety of extracellular stimuli, such as cellular stresses and growth factors, to regulate processes such as cell proliferation and differentiation. Targeted deletion of Erk5 in mice has revealed that the ERK5 signalling cascade plays a critical role in cardiovascular development and vascular integrity. Recent data points to a potential role in pathological conditions such as cancer and tumour angiogenesis. This review focuses on the physiological and pathological role of ERK5, the regulation of this kinase and the recent development of small molecule inhibitors of the ERK5 signalling cascade.
MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Gopika N
GN
Nithianandarajah-Jones
Bettina
B
Wilm
Christopher E P
CE
Goldring
Jürgen
J
Müller
Michael J
MJ
Cross
D000818:Animals; D035683:MicroRNAs / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry; D015398:Signal Transduction
D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases