Difference between revisions of "Phosphatase Subfamily PTPRG"

Revision as of 16:59, 14 September 2015

Phosphatase Classification: Fold CC1:Superfamily CC1: Family PTP: Subfamily PTPRG

PTPRG is a receptor PTP subfamily involved in eumetazoan neural development and maybe cancer.

Evolution

The PTPRG subfamily is found in eumetazoans, typically single-copy, but expanded to two genes, PTPRG and PTPRZ in human and other vertebrates.

Domain

These are receptor PTPs with dual intracellular catalytic domains. The extracellular domain contains at least one FN3 domain. Vertebrate members have a catalytically inactive carbonic anhydrase (CA) domain, while most invertebrates, including one invertebrate chordate, have additional Ig and FN3 repeats instead. The CA domain acts as a receptor for members of the contactin family of neural cell adhesion molecules [1].

Functions

The vertebrate forms are expressed in brain and involved in cell adhesion. Drosophila ptp99a is also selectively expressed and functions in the nervous system, interacting with other RPTPs, including Dlar and ptp69D.

PTPRG is suggested to be a tumor suppressor due to it's frequent loss or decreased expression in a number of cancer types.

The phosphatase activity is modulated by the ligands binding to extracellular region [2] and other proteins binding to the cytoplasmic region [3].

PTPRG has various isoforms. Peptides from its extracellular domain have been detected in plasma by proteomic techniques, and a natural soluble protein in plasma has been identified by experimental assays [4].

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

Here are the unorganized notes on functions.

References

1. Bouyain S and Watkins DJ. The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2443-8. DOI:10.1073/pnas.0911235107 | PubMed ID:20133774 | HubMed [Bouyain]
2. Mohebiany AN, Nikolaienko RM, Bouyain S, and Harroch S. Receptor-type tyrosine phosphatase ligands: looking for the needle in the haystack. FEBS J. 2013 Jan;280(2):388-400. DOI:10.1111/j.1742-4658.2012.08653.x | PubMed ID:22682003 | HubMed [Mohebiany13]
3. Shen X, Xi G, Wai C, and Clemmons DR. The coordinate cellular response to insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-2 (IGFBP-2) is regulated through vimentin binding to receptor tyrosine phosphatase β (RPTPβ). J Biol Chem. 2015 May 1;290(18):11578-90. DOI:10.1074/jbc.M114.620237 | PubMed ID:25787077 | HubMed [Shen15]
4. Moratti E, Vezzalini M, Tomasello L, Giavarina D, and Sorio C. Identification of protein tyrosine phosphatase receptor gamma extracellular domain (sPTPRG) as a natural soluble protein in plasma. PLoS One. 2015;10(3):e0119110. DOI:10.1371/journal.pone.0119110 | PubMed ID:25775014 | HubMed [Moratti15]
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]