Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling.
Dual-specificity MAP kinase phosphatases (MKPs) provide a complex negative regulatory network that acts to shape the duration, magnitude and spatiotemporal profile of MAP kinase activities in response to both physiological and pathological stimuli. Individual MKPs may exhibit either exquisite specificity towards a single mitogen-activated protein kinase (MAPK) isoform or be able to regulate multiple MAPK pathways in a single cell or tissue. They can act as negative feedback regulators of MAPK activity, but can also provide mechanisms of crosstalk between distinct MAPK pathways and between MAPK signalling and other intracellular signalling modules. In this review, we explore the current state of knowledge with respect to the regulation of MKP expression levels and activities, the mechanisms by which individual MKPs recognize and interact with different MAPK isoforms and their role in the spatiotemporal regulation of MAPK signalling.
Department of Biology and Biochemistry, University of Bath, Bath, UK. c.caunt@bath.ac.uk
Christopher J
CJ
Caunt
Stephen M
SM
Keyse
D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D054642:Dual Specificity Phosphatase 6 / Q000378:metabolism; D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D013379:Substrate Specificity
D020928:Mitogen-Activated Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C442320:DUSP5 protein, human; C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6; D054637:Dual-Specificity Phosphatases