Protein phosphatases and the regulation of mitogen-activated protein kinase signalling.
The magnitude and duration of signalling through mitogen- and stress-activated kinases are critical determinants of biological effect. This reflects a balance between the activities of upstream activators and a complex regulatory network of protein phosphatases. These mitogen-activated protein kinase phosphatases include both dual-specificity (threonine/tyrosine) and tyrosine-specific enzymes, and recent evidence suggests that a single mitogen-activated protein kinase isoform may be acted upon by both classes of protein phosphatase. In both cases, substrate selectivity is determined by specific protein-protein interactions mediated through noncatalytic amino-terminal mitogen-activated protein kinase binding domains. Future challenges include the determination of exactly how this network of protein phosphatases interacts selectively with mitogen-activated protein kinase signalling complexes to achieve precise regulation of these key pathways in mammalian cells.
Keyse
S M
SM
Molecular Pharmacology Unit, Imperial Cancer Research Fund, Biomedical Research Centre, Level 5, Ninewells Hospital, Dundee, DD1 9SY, UK. S.Keyse@icrf.icnet.uk
D000818:Animals; D002384:Catalysis; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008934:Mitogens / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism* / Q000502:physiology; D013379:Substrate Specificity
D007527:Isoenzymes; D008934:Mitogens; D017027:Protein Tyrosine Phosphatases