Role of MAP Kinase Phosphatase-1 in health and disease

Abstract

Mitogen-activated signaling pathways (MAPK) are one of the major and evolutionary conserved signaling pathways involved in protein phosphorylation. Inactivation of MAPK activity is attained by dephosphorylation of either the tyrosine or threonine residues, or both by the actions of MAP kinase phosphatase (MKPs). The prototype member of MKP family, MKP-1 is the most extensively studied MKP compared to ten other members in the group. Several mouse genetic and in vitro studies have established a key role for MKP-1 in the immune and metabolic systems. However, more recently there is growing body of literature suggesting important functions in the cardiovascular, nervous and musculoskeletal systems. With the development of tissue-specific knock-out models most of these studies suggest MKP- 1 as potential therapeutic target in many disease conditions. Abbreviations: MAPK, mitogen-activated protein kinase; DUSP, dual-specificity phosphatase; MKP, MAP kinase phosphatase; ERK, extracellular-signal-regulated kinase; JNK, c-jun N-terminal kinase; hVH, human vaccinia H1 phosphatase; PAC-1, phosphatase of activated cell 1:MKB,MAPK-binding.

Keywords: Dual-specificity phosphatase (DUSP), MAP kinase phosphatases (MKPs), Knock-out mice, mitogen-activated protein kinase (MAPK), immunity, metabolism