Protein Phosphatase of Ciona savignyi
• DSP groupThere are 18 phosphatases exist in 7 families
aDSP (1) aDSP (Atypical DSP) family contains phosphatases which are poorly characterized. They are smaller than MKP family and lack specific MAP kinase motifs (1). Family member DUSP3 is invloved in down-regulating the ERK pathway and specifically dephosphorylates and inactivates ERK1 and ERK2 (2). DUSP11 shows phosphatase activity towards RNA 5'-triphosphatase and may participate in nuclear mrna metabolism. The studies show that most of aDSP phosphatase have function unrelated to MAP kinases (3).
Reference
1. Alonso, A., Sasin, J., Bottini, N., Friedberg, I., Osterman, A., Godzik, A., Hunter, T., Dixon, J. and Mustelin, T. (2004) Protein tyrosine phosphatases in the human genome. Cell, 117, 699-711. PMID:15186772 2. Todd, J.L., Tanner, K.G. and Denu, J.M. (1999) 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, 13271-13280. PMID: 10224087 3. Yuan, Y., Li, D.M. and Sun, H. (1998) PIR1, a novel phosphatase that exhibits high affinity to RNA . ribonucleoprotein complexes. J Biol Chem, 273, 20347-20353. PMID: 9685386 | CDC14 (1) CDC14 phosphatase belongs to a family of highly conserved DUSP phosphatases. All CDC14 family members share a conserved N-terminal core domain, in which two subdomains contribute to critical function, one is involved in substrate specificity and another subdomain acts as the phosphatase catalytic domain. The C-terminal domain of CDC14 family is variable which might be involved in subcellular localization. Protein phosphatases of CDC14 family are key regulators in cell cycle and they are characterized by controlling exit from mitosis. CDC14 is well understood in budding yeast Saccharomyces cerevisiae and studies show that ScCDC14 plays an important role in DNA replication, mitotic exit and cytokinesis. In Saccharomyces pombe CDC14-Like phosphatase, also known as Clp1, participates in G2−M transition and cytokinesis. In mammals, human CDC14B is important in regulating centriole duplication, cell cycle progression, mitotic exit, DNA damage and DNA repair (1).
Reference
1. Mocciaro, A. and Schiebel, E. (2010) Cdc14: a highly conserved family of phosphatases with non-conserved functions? J Cell Sci, 123, 2867-2876. PMID: 20720150 | MKP (7) MAPK phosphatase (MKP) is a large family of dual-specificity phosphatases. The family members are characterized by the C-terminal catalytic domains which share the sequence similarity with prototypic dual-specificity protein phosphatase VH-1 and the N-terminal domain contains two regions of sequence similarity to the catalytic domain of the Cdc25 phosphatase. MKP is involved in varieties of cellular processes. DUSP10/MKP-5 can negatively regulate the JNK signaling pathway and plays an important role in negatively regulating innate immune responses and proper T cell function. In addition, DUSP10/MKP-5 can regulate p38 MAPK activity. DUSP1/MKP-1 is involved in regulating metabolic by dephosphorylating its MAPK substrates. DUSP9/MKP-4 plays a critical role in placental development and function. DUSP6/MKP-3 acts as a negative feedback regulator of fibroblast growth factor signaling (1).
Reference
1. Dickinson, R.J. and Keyse, S.M. (2006) Diverse physiological functions for dual-specificity MAP kinase phosphatases. J Cell Sci, 119, 4607-4615. PMID: 17093265 | Myotubularins (5) Myotubularins (MTM) phosphatases belong to a family of conserved DUSP phosphatase. The myotubularins is consist of 14 members which share a conserved protein tyrosine phosphatase catalytic domain and myotubularins is a large family of phosphoinositide lipid 3-phosphatases with specificity for PtdIns3P and PtdIns (3, 5) P2. Besides PTP domain, myotubularins also contains other motifs which may contribute to protein−protein or protein−lipid interactions. Myotubularins participates in endocytic pathway by regulating substrates PtdIns3P and PtdIns (3,5)P2 which are key regulator of endocytic pathway and myotubularins may function to suppress concentration of substrate lipids at inappropriate compartments. In addition, some studies show that several MTMs, such as MTMR1, MTMR6, MTMR7, MTMR8 and MTMR12 play an important role in promoting cell survival by regulating PtdIns5P level and PtdIns (3,4,5)P3 specific 5-phosphatase, in turn control PKB/Akt activation. Myotubularins mutation is often accompanied with some diseases. MTM1 mutation can lead to condition known as myotubular myopathy. MTMR2 and MTMR13/Sbf2 mutations lead to clinically indistinguishable forms of a neuropathy called Charcot−Marie−Tooth syndrome (types 4B1 and 4B2). MTMR2 and MTMR5/Sbf1 mutations lead to impaired spermatogenesis and azoospermia.
Reference
1. Clague, M.J. and Lorenzo, O. (2005) The myotubularin family of lipid phosphatases. Traffic, 6, 1063-1069. PMID: 16262718 | PRL (1) Phosphatases of regenerating liver known as PRL family belong to DUSP family. PRL contains three family members PRL-1, PRL-2 and PRL-3. The N-terminal catalytic domain of PRL contains a CXXXXXR motif which is critical feature in tyrosine phosphatase responsible for catalytic activity. In addition, all PRL members contain a COOH-terminal CAAX motif and they can be post-translationally farnesylated, which suggests that PRL localize to membrane structures. PRL-3 is expressed in heart and PRL-1 and PRL-2 are expressed ubiquitously in various tissues which indicate that PRL members are involved in varieties of functions. PRL family plays an important role in proliferation and transforms nontumorigenic immortalized cell lines. In addition, PRLs also play a key role in metastasis and control cell cycle. What's more, PRLs are highly expressed in several tumor tissues and cell lines, which might suggests they correlate with some disease (1).
Reference
1. 1. Camps, M., Nichols, A. and Arkinstall, S. (2000) Dual specificity phosphatases: a gene family for control of MAP kinase function. FASEB J, 14, 6-16. PMID: 10627275 |
PTEN (2) PTEN (phosphatase and tensin homolog deleted on chromosome ten) phosphatase is a conserved family of DUSP phosphatase, which could dephosphorylate tyrosine-, serine- and threonine-phosphorylated proteins. PTEN also acts as lipid phosphatase, which dephosphorylates D3-phosphorylated inositol phospholopids (1). PTEN negatively regulates PI3 kinase-Akt signaling pathway by converting second messenger phosphatidylinositol 3,4,5-triphosphate (PIP3) into phosphatidylinositol 4,5-bisphosphate (PIP2). This pathway plays an important role in controlling cell proliferation, growth and survival (2). In addition to its dominant inhibitory activity in the PI3 kinase-Akt pathway, PTEN also possess potential protein phosphatase activity for its sequence similarity with PTP domain and this remains more understood.
Reference
1. Patterson, K.I., Brummer, T., O'Brien, P.M. and Daly, R.J. (2009) Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J, 418, 475-489. PMID: 19228121 2. Wang, X. and Jiang, X. (2008) PTEN: a default gate-keeping tumor suppressor with a versatile tail. Cell Res, 18, 807-816. PMID: 18626510 | SSH (1) Slingshot is a family of DUSP protein phosphatase and contains three members in human genome, which are known as SSH1, SSH2 and SSH3. SSH phosphatase mainly functions as regulators of actin filament dynamics through dephosphorylating cofilin. Dephosphorylation of cofilin stimulates its activity and then cofilin binds to F-Actin, stimulates F-actin depolymerization and severing (1). In addition, SSH phosphatase and LIMK play an important role in directing cell migration (2).
Reference
1. Huang, T.Y., DerMardirossian, C. and Bokoch, G.M. (2006) Cofilin phosphatases and regulation of actin dynamics. Curr Opin Cell Biol, 18, 26-31. PMID: 16337782 2. Nishita, M., Tomizawa, C., Yamamoto, M., Horita, Y., Ohashi, K. and Mizuno, K. (2005) Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration. J Cell Biol, 171, 349-359. PMID: 16230460 |
※ Family introduction