InterPro domain: IPR020420

The atypical DUSPs share a high degree of similarity with the MKP subgroup, but lack the N-terminal regulatory domain, which provides the substrate specificity towards the MAP kinases. These atypical-DUSPs form a heterogeneous group and have in common the presence of a single catalytic PTP domain. VHR was the first characterised member of this subfamily; its crystal structure is known [ 1 , 2 ].

The function of many atypical DUSPs remains unknown, although some have been related to regulation of MAP kinase pathways [ 3 , 4 , 5 ]. VHR has also been related to the control of cell-senescence [ 6 ].

The atypical DUSPs can be subdivided into two groups (termed A and B) on the basis of sequence similarity. Each of these subgroups is characterised by its own distinctive set of motifs, the functions of which are as yet unknown.

This entry also includes DUSP1 which does not belong to the atypical DUSP family.

Dual specificity phosphatases (DUSPs) are members of the superfamily of protein tyrosine phosphatases [ 7 , 8 ]. They remove the phosphate group from both phospho-tyrosine and phospho-serine/threonine residues. They are structurally similar to tyrosine-specific phosphatases but with a shallower active site cleft and a distinctive active site signature motif, HCxxGxxR [ 9 , 10 , 11 ]. They are characterized as VHR- [ 12 , 13 ] or Cdc25-like [ 13 , 14 ].

In general, DUSPs are classified into the following subgroups [ 15 ]:

• Slingshot phosphatases
• Phosphatase of regenerating liver (PRL)
• Cdc14 phosphatases
• Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-like and myotubularin phosphatases
• Mitogen-activated protein kinase phosphatases (MKPs)
• Atypical DUSPs

1. Expression cloning of a human dual-specificity phosphatase. Proc. Natl. Acad. Sci. U.S.A. 89, 12170-4
2. Crystal structure of the dual specificity protein phosphatase VHR. Science 272, 1328-31
3. Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway. J. Biol. Chem. 274, 13271-80
4. Dual-specificity protein tyrosine phosphatase VHR down-regulates c-Jun N-terminal kinase (JNK). Oncogene 21, 2573-83
5. MKP-8, a novel MAPK phosphatase that inhibits p38 kinase. Biochem. Biophys. Res. Commun. 330, 511-8
6. Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence. Nat. Cell Biol. 8, 524-31
7. Protein tyrosine phosphatases: from genes, to function, to disease. Nat. Rev. Mol. Cell Biol. 7, 833-46
8. Protein tyrosine phosphatases in the human genome. Cell 117, 699-711
9. Structure and function of the protein tyrosine phosphatases. Trends Biochem. Sci. 21, 413-7
10. The catalytic role of Cys124 in the dual specificity phosphatase VHR. J. Biol. Chem. 269, 28084-90
11. Protein tyrosine phosphatases: mechanism of catalysis and substrate specificity. Adv. Enzymol. Relat. Areas Mol. Biol. 68, 1-36
12. The "VH1-like" dual-specificity protein tyrosine phosphatases. Mol. Cells 8, 2-11
13. Cloning and sequencing of a pig cdc25 tyrosine phosphatase cDNA. J. Anim. Sci. 73, 630
14. Protein tyrosine phosphatases: their roles in signal transduction. Recent Prog. Horm. Res. 51, 405-14; discussion 415
15. Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem. J. 418, 475-89