title: Mitogen-activated protein kinase phosphatase-1: a critical phosphatase manipulating mitogen-activated protein kinase signaling in cardiovascular disease (review).
abstract: Mitogen-activated protein kinase (MAPK) cascades are important players in the overall representation of cellular signal transduction pathways, and the deregulation of MAPKs is involved in a variety of diseases. The activation of MAPK signals occurs through phosphorylation by MAPK kinases at conserved threonine and tyrosine (Thr-Xaa-Tyr) residues. The mitogen-activated protein kinase phosphatases (MKPs) are a major part of the dual-specificity family of phosphatases and speciﬁcally inactivate MAPKs by dephosphorylating both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate. MAPKs binding to MKPs can enhance MKP stability and activity, providing an important negative-feedback control mechanism that limits the MAPK cascades. In recent years, accumulating and compelling evidence from studies mainly employing cultured cells and mouse models has suggested that the archetypal MKP family member, MKP-1, plays a pivotal role in cardiovascular disease as a major negative modulator of MAPK signaling pathways. In the present review, we summarize the current knowledge on the pathological properties and the regulation of MKP-1 in cardiovascular disease, which may provide valuable therapeutic options.
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Ling-Chao
authors.initials: LC
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Yue-Peng
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Yi-Gang
authors.initials: YG
authors.lastname: Li
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System
chemical_list: D054638:Dual Specificity Phosphatase 1