Diversity and specificity of the mitogen-activated protein kinase phosphatase-1 functions.
The balance of protein phosphorylation is achieved through the actions of a family of protein serine/threonine kinases called the mitogen-activated protein kinases (MAPKs). The propagation of MAPK signals is attenuated through the actions of the MAPK phosphatases (MKPs). The MKPs specifically inactivate the MAPKs by direct dephosphorylation. The archetypal MKP family member, MKP-1 has garnered much of the attention amongst its ten other MKP family members. Initially viewed to play a redundant role in the control of MAPK signaling, it is now clear that MKP-1 exerts profound regulatory functions on the immune, metabolic, musculoskeletal and nervous systems. This review focuses on the physiological functions of MKP-1 that have been revealed using mouse genetic approaches. The implications from studies using MKP-1-deficient mice to uncover the role of MKP-1 in disease will be discussed.
Department of Pharmacology, Yale University School of Medicine, SHM B226D, 333 Cedar Street, New Haven, CT 06520-8066, USA.
Ahmed
A
Lawan
Hao
H
Shi
Florian
F
Gatzke
Anton M
AM
Bennett
D000818:Animals; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction
D020928:Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse