%0 Journal Article
%T DUSPs, to MAP kinases and beyond
%A Ching-Yu Huang
%A Tse-Hua Tan
%J Cell & Bioscience
%D 2012
%I BioMed Central
%R 10.1186/2045-3701-2-24
%X The dual-specificity phosphatase (DUSP) family proteins are so named for their ability to dephosphorylate both the threonine/serine and tyrosine residues of their substrates. This ability may be attributed to their shallow and flexible enzymatic pockets, which can accommodate both types of phosphorylated residues. Structure-wise, all DUSPs contain a common phosphatase domain with conserved aspartic acid, cysteine, and arginine residues forming the catalytic site. A subset of DUSPs contains an N-terminal region composed of two CDC25 homology 2 domains and an intervening cluster of basic amino acids known as the MAP kinase-binding (MKB) motif or kinase-interacting motif (KIM); this MKB/KIM motif of DUSP interacts with the common domain (CD) of MAP kinases to mediate the enzyme-substrate interaction. Some DUSPs also contain a C-terminal PEST domain or additional N- or C-terminal domains; but the functions of those domains are not well characterized (Figure 1) [1].There are currently 25 genes in the Human Genome Organization database designated as DUSPs, namely DUSP1-28 ¡ª with DUSP17-20, and £¿23 redundantly assigned as DUSP19-18, and £¿25, respectively. Within the 25 DUSPs, MS-STYX/DUSP24 and DUSP27 do not contain the conserved cysteine residue for nucleophilic attack (C to S substitution) and thus lack phosphatase activity (Figure 1). These 25 DUSPs can be partitioned, based on their amino acid alignment, into those that contain the MKB/KIM domain and those that do not. DUSPs missing the MKB/KIM domain are generally grouped as atypical DUSPs, while MKB/KIM-containing DUSPs are generally grouped as typical DUSPs or MAP kinase phosphatases (MKPs) (Figure 2). However, there are a few exceptions, with MKP6/DUSP14, JKAP/DUSP22, and MKP8/DUSP26 actually being atypical DUSPs without the KIM domain, and KIM-containing PAC1/DUSP2, HVH3/DUSP5, and HVH-5/DUSP8 not receiving MKP designation (Figure 1). Typical DUSPs can be further divided into three groups based on their predominan
%K Phosphatase
%K DUSP
%K Signal Transduction
%K T Cell Development
%K Immune Regulation
%U http://www.cellandbioscience.com/content/2/1/24