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.