Phosphatase Subfamily DSP6

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP6

Function

DUSP7 (MKPX/PYST2)

DUSP7 is constitutively expressed in a wide variety of human cell lines. DUSP7 is predominantly cytosolic when expressed in COS-1 cells. In common with other members of DSP6 subfamily, DUSP7 shows substrate selectivity ERK > p38 = JNK. DUSP7 binds ERK in vivo. Both ERK and JNK activate DUSP7 phosphatase activity in vitro [1].

DUSP7 has at least two isoforms. The longer isoform is constitutively highly expressed in myeloid leukemia and other malignant cells [2, 3, 4].

DUSP9 (MKP4)

DUSP6 blocks activation of MAP kinases with the selectivity ERK > p38 = JNK. Same as other members in the subfamily, it locates in cytosol [5, 6]. DUSP9 is unique among these cytoplasmic MKPs in containing a conserved PKA consensus phosphorylation site (55)RRXSer-58 immediately adjacent to the kinase interaction motif. DUSP9 is phosphorylated on Ser-58 by PKA in vitro, and phosphorylation abrogates the binding of DUSP9 to both ERK2 and p38alpha MAP kinases [7].

Decreased expression of DUSP-9 is associated with poor prognosis in clear cell renal cell carcinomas [8].

References

2. Levy-Nissenbaum O, Sagi-Assif O, Kapon D, Hantisteanu S, Burg T, Raanani P, Avigdor A, Ben-Bassat I, and Witz IP. Dual-specificity phosphatase Pyst2-L is constitutively highly expressed in myeloid leukemia and other malignant cells. Oncogene. 2003 Oct 23;22(48):7649-60. DOI:10.1038/sj.onc.1206971 |
3. Levy-Nissenbaum O, Sagi-Assif O, Raanani P, Avigdor A, Ben-Bassat I, and Witz IP. cDNA microarray analysis reveals an overexpression of the dual-specificity MAPK phosphatase PYST2 in acute leukemia. Methods Enzymol. 2003;366:103-13. DOI:10.1016/s0076-6879(03)66009-x |
4. Levy-Nissenbaum O, Sagi-Assif O, and Witz IP. Characterization of the dual-specificity phosphatase PYST2 and its transcripts. Genes Chromosomes Cancer. 2004 Jan;39(1):37-47. DOI:10.1002/gcc.10295 |
5. Muda M, Boschert U, Smith A, Antonsson B, Gillieron C, Chabert C, Camps M, Martinou I, Ashworth A, and Arkinstall S. Molecular cloning and functional characterization of a novel mitogen-activated protein kinase phosphatase, MKP-4. J Biol Chem. 1997 Feb 21;272(8):5141-51. DOI:10.1074/jbc.272.8.5141 |
6. Liu Y, Lagowski J, Sundholm A, Sundberg A, and Kulesz-Martin M. Microtubule disruption and tumor suppression by mitogen-activated protein kinase phosphatase 4. Cancer Res. 2007 Nov 15;67(22):10711-9. DOI:10.1158/0008-5472.CAN-07-1968 |
7. Dickinson RJ, Delavaine L, Cejudo-Marín R, Stewart G, Staples CJ, Didmon MP, Trinidad AG, Alonso A, Pulido R, and Keyse SM. Phosphorylation of the kinase interaction motif in mitogen-activated protein (MAP) kinase phosphatase-4 mediates cross-talk between protein kinase A and MAP kinase signaling pathways. J Biol Chem. 2011 Nov 4;286(44):38018-38026. DOI:10.1074/jbc.M111.255844 |
8. Wu S, Wang Y, Sun L, Zhang Z, Jiang Z, Qin Z, Han H, Liu Z, Li X, Tang A, Gui Y, Cai Z, and Zhou F. Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma. BMC Cancer. 2011 Sep 26;11:413. DOI:10.1186/1471-2407-11-413 |
9. Muda M, Boschert U, Dickinson R, Martinou JC, Martinou I, Camps M, Schlegel W, and Arkinstall S. MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase. J Biol Chem. 1996 Feb 23;271(8):4319-26. DOI:10.1074/jbc.271.8.4319 |