Difference between revisions of "Phosphatases and Diseases"

Revision as of 16:16, 11 April 2017

Main_Page Main: Phosphatases and Diseases

Phosphatases co-regulate most biological processes with kinases, and like kinases, when dysregulation or mutation of phosphatases leads to a wide variety of diseases.

Cancer

PTPRA

A PTPRA splice mutant activated Src is found in human tumours [1].

PTEN

PTPN11 (SHP2)

PTPRC (CD45)

DUSP3 (VHR)

DUSP3 is a negative regulator of ERK and JNK pathways in in vitro studies in several cell lines. Though its role is involved in human cancer, its has contradictory roles since it has been alternatively described as having tumor suppressive and oncogenic properties [2].

DUSP26 (MKP8)

DUSP26 (aka MKP8) is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma [3].

PPM1D (WIP1)

PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas [4].

PTPRZ1

PTPRZ1-MET (ZM) fusion protein induces gliomas through elevated expression and phosphorylation of the MET oncoprotein [5]. The fusion protein is found in human gliomas by high-throughput sequencing.

Parkinson's disease

DNAJC6

See OMIM.

Other diseases

MTMR3: Inflammatory bowel disease (IBD)

The rs713875 IBD risk polymorphism increases MTMR3 expression.

PDP1: pyruvate dehydrogenase (PDH) deficiency

See OMIM.

SBF1: Charcot-Marie-Tooth disease

See OMIM.

PPM1K: maple syrup urine disease

See OMIM.

MTMR14: centronuclear myopathy

See OMIM.

PTPRQ: deafness

See OMIM.

References

1. Huang J, Yao L, Xu R, Wu H, Wang M, White BS, Shalloway D, and Zheng X. Activation of Src and transformation by an RPTPα splice mutant found in human tumours. EMBO J. 2011 Jul 1;30(15):3200-11. DOI:10.1038/emboj.2011.212 | PubMed ID:21725282 | HubMed [Huang11]
2. Amand M, Erpicum C, Bajou K, Cerignoli F, Blacher S, Martin M, Dequiedt F, Drion P, Singh P, Zurashvili T, Vandereyken M, Musumeci L, Mustelin T, Moutschen M, Gilles C, Noel A, and Rahmouni S. DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase. Mol Cancer. 2014 May 15;13:108. DOI:10.1186/1476-4598-13-108 | PubMed ID:24886454 | HubMed [Rahmouni14]
3. Shang X, Vasudevan SA, Yu Y, Ge N, Ludwig AD, Wesson CL, Wang K, Burlingame SM, Zhao YJ, Rao PH, Lu X, Russell HV, Okcu MF, Hicks MJ, Shohet JM, Donehower LA, Nuchtern JG, and Yang J. Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma. Oncogene. 2010 Sep 2;29(35):4938-46. DOI:10.1038/onc.2010.244 | PubMed ID:20562916 | HubMed [yangj10]
4. Zhang L, Chen LH, Wan H, Yang R, Wang Z, Feng J, Yang S, Jones S, Wang S, Zhou W, Zhu H, Killela PJ, Zhang J, Wu Z, Li G, Hao S, Wang Y, Webb JB, Friedman HS, Friedman AH, McLendon RE, He Y, Reitman ZJ, Bigner DD, and Yan H. Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas. Nat Genet. 2014 Jul;46(7):726-30. DOI:10.1038/ng.2995 | PubMed ID:24880341 | HubMed [yan14]
5. Chen HM, Yu K, Tang XY, Bao ZS, Jiang T, Fan XL, Chen XW, and Su XD. Enhanced expression and phosphorylation of the MET oncoprotein by glioma-specific PTPRZ1-MET fusions. FEBS Lett. 2015 Jun 4;589(13):1437-43. DOI:10.1016/j.febslet.2015.04.032 | PubMed ID:25935522 | HubMed [Chen15]