Phosphatase Subfamily PTPRK

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

PTPRG is a receptor PTP family involved in metazoan neural development and maybe cancer.

Evolution

PTPRK subfamily is vertebrate specific. There are four copies in human.

Domain Structure

PTPRK has dual intracellular catalytic domains. The canonical extracellular domain combination (PTPRK, PTPRM, PTPRU) is a MAM domain, 1 Ig domain and 4 FN3 domain.

MAM domain is essential for homophilic cell-cell interaction and helps determine the specificity of these interactions. Truncated PTPRM is properly expressed at the cell surface but fails to promote cell-cell adhesion. Homophilic cell adhesion is fully restored in a chimeric PTPRM molecule containing the MAM domain of PTPRK. However, this chimeric RPTP mu does not interact with either PTPRK or PTPRM [1].

Functions

PTPRK subfamily mediates homophilic cell-cell interaction [1, 2, 3].

PTPRK

PTPRK is a putative tumor suppressor [4] in various types of cancer, such as breast cancer [5], prostate cancer [6], lymphoma [7] and glioma [8]. It plays its function as tumor suppressor through different mechanisms. PTPRK influences transactivating activity of beta-catenin in non-tumoral and neoplastic cells by regulating the balance between signaling and adhesive beta-catenin which is a molecule endowed with a dual function being involved both in cell adhesion and in Wnt signaling pathway [9]. PTPRK is a key factor in coordinating apoptosis via the regulation of MAPK pathways, in particular the JNK pathway in prostate cancer cells [6]. PTPRK dephosphorylates Epidermal growth factor receptor (EGFR) and thereby regulates EGFR tyrosine phosphorylation and subsequent promotes human keratinocyte survival and proliferation [10]. It is worthy pointing out that PTPRK is the target of transforming growth factor {beta} (TGF-{beta})-Smad, which inhibits proliferation and promotes cell migration [7, 11, 12].

PTPRK also dephosphorylates Src [12].

PTPRK regulates CD4+ T cell development through ERK1/2-mediated signaling [13].

References

1. Zondag GC, Koningstein GM, Jiang YP, Sap J, Moolenaar WH, and Gebbink MF. Homophilic interactions mediated by receptor tyrosine phosphatases mu and kappa. A critical role for the novel extracellular MAM domain. J Biol Chem. 1995 Jun 16;270(24):14247-50. DOI:10.1074/jbc.270.24.14247 |
2. Sap J, Jiang YP, Friedlander D, Grumet M, and Schlessinger J. Receptor tyrosine phosphatase R-PTP-kappa mediates homophilic binding. Mol Cell Biol. 1994 Jan;14(1):1-9. DOI:10.1128/mcb.14.1.1-9.1994 |
4. Zhang Y, Siebert R, Matthiesen P, Yang Y, Ha H, and Schlegelberger B. Cytogenetical assignment and physical mapping of the human R-PTP-kappa gene (PTPRK) to the putative tumor suppressor gene region 6q22.2-q22.3. Genomics. 1998 Jul 15;51(2):309-11. DOI:10.1006/geno.1998.5323 |
5. Sun PH, Ye L, Mason MD, and Jiang WG. Protein tyrosine phosphatase kappa (PTPRK) is a negative regulator of adhesion and invasion of breast cancer cells, and associates with poor prognosis of breast cancer. J Cancer Res Clin Oncol. 2013 Jul;139(7):1129-39. DOI:10.1007/s00432-013-1421-5 |
6. Sun PH, Ye L, Mason MD, and Jiang WG. Receptor-like protein tyrosine phosphatase κ negatively regulates the apoptosis of prostate cancer cells via the JNK pathway. Int J Oncol. 2013 Nov;43(5):1560-8. DOI:10.3892/ijo.2013.2082 |
7. Flavell JR, Baumforth KR, Wood VH, Davies GL, Wei W, Reynolds GM, Morgan S, Boyce A, Kelly GL, Young LS, and Murray PG. Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells. Blood. 2008 Jan 1;111(1):292-301. DOI:10.1182/blood-2006-11-059881 |
9. Xu Y, Tan LJ, Grachtchouk V, Voorhees JJ, and Fisher GJ. Receptor-type protein-tyrosine phosphatase-kappa regulates epidermal growth factor receptor function. J Biol Chem. 2005 Dec 30;280(52):42694-700. DOI:10.1074/jbc.M507722200 |
10. Xu Y, Tan LJ, Grachtchouk V, Voorhees JJ, and Fisher GJ. Receptor-type protein-tyrosine phosphatase-kappa regulates epidermal growth factor receptor function. J Biol Chem. 2005 Dec 30;280(52):42694-700. DOI:10.1074/jbc.M507722200 |
11. Yang Y, Gil M, Byun SM, Choi I, Pyun KH, and Ha H. Transforming growth factor-beta1 inhibits human keratinocyte proliferation by upregulation of a receptor-type tyrosine phosphatase R-PTP-kappa gene expression. Biochem Biophys Res Commun. 1996 Nov 21;228(3):807-12. DOI:10.1006/bbrc.1996.1736 |
12. Wang SE, Wu FY, Shin I, Qu S, and Arteaga CL. Transforming growth factor {beta} (TGF-{beta})-Smad target gene protein tyrosine phosphatase receptor type kappa is required for TGF-{beta} function. Mol Cell Biol. 2005 Jun;25(11):4703-15. DOI:10.1128/MCB.25.11.4703-4715.2005 |
13. Erdenebayar N, Maekawa Y, Nishida J, Kitamura A, and Yasutomo K. Protein-tyrosine phosphatase-kappa regulates CD4+ T cell development through ERK1/2-mediated signaling. Biochem Biophys Res Commun. 2009 Dec 18;390(3):489-93. DOI:10.1016/j.bbrc.2009.09.117 |
14. Agarwal S, Al-Keilani MS, Alqudah MA, Sibenaller ZA, Ryken TC, and Assem M. Tumor derived mutations of protein tyrosine phosphatase receptor type k affect its function and alter sensitivity to chemotherapeutics in glioma. PLoS One. 2013;8(5):e62852. DOI:10.1371/journal.pone.0062852 |
15. Kim YS, Jung JA, Kim HJ, Ahn YH, Yoo JS, Oh S, Cho C, Yoo HS, and Ko JH. Galectin-3 binding protein promotes cell motility in colon cancer by stimulating the shedding of protein tyrosine phosphatase kappa by proprotein convertase 5. Biochem Biophys Res Commun. 2011 Jan 7;404(1):96-102. DOI:10.1016/j.bbrc.2010.11.071 |