Receptor tyrosine phosphatases (RTP)- also referred to as receptor-type tyrosine-protein phosphatases (PTPR) - are cell-surface proteins with a single TM region and intracellular phosphatase activity at phosphorylated tyrosine residues. There are 20 family members of classic RPTPs. Many family members exhibit constitutive activity upon heterologous expression, dephosphorylating intracellular targets such as Src tyrosine kinase (SRC) to activate signalling cascades. Family members bind components of the extracellular matrix or cell-surface proteins indicating a role in intercellular communication.

* Key recommended reading is highlighted with an asterisk

Bouyain S, Watkins DJ. (2010) The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules. Proc Natl Acad Sci USA, 107 (6): 2443-8. [PMID:20133774]

Böhmer F, Szedlacsek S, Tabernero L, Ostman A, den Hertog J. (2013) Protein tyrosine phosphatase structure-function relationships in regulation and pathogenesis. FEBS J, 280 (2): 413-31. [PMID:22682070]

Dushek O, Goyette J, van der Merwe PA. (2012) Non-catalytic tyrosine-phosphorylated receptors. Immunol Rev, 250 (1): 258-76. [PMID:23046135]

Granot-Attas S, Elson A. (2008) Protein tyrosine phosphatases in osteoclast differentiation, adhesion, and bone resorption. Eur J Cell Biol, 87 (8-9): 479-90. [PMID:18342392]

Hendriks WJ, Dilaver G, Noordman YE, Kremer B, Fransen JA. (2009) PTPRR protein tyrosine phosphatase isoforms and locomotion of vesicles and mice. Cerebellum, 8 (2): 80-8. [PMID:19137382]

Hermiston ML, Zikherman J, Zhu JW. (2009) CD45, CD148, and Lyp/Pep: critical phosphatases regulating Src family kinase signaling networks in immune cells. Immunol Rev, 228 (1): 288-311. [PMID:19290935]

Julien SG, Dubé N, Hardy S, Tremblay ML. (2011) Inside the human cancer tyrosine phosphatome. Nat Rev Cancer, 11 (1): 35-49. [PMID:21179176]

Kim YS, Jung JA, Kim HJ, Ahn YH, Yoo JS, Oh S, Cho C, Yoo HS, Ko JH. (2011) 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, 404 (1): 96-102. [PMID:21094132]

Kwon SK, Woo J, Kim SY, Kim H, Kim E. (2010) Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma via specific domains regulate excitatory synapse formation. J Biol Chem, 285 (18): 13966-78. [PMID:20139422]

Meng K, Rodriguez-Peña A, Dimitrov T, Chen W, Yamin M, Noda M, Deuel TF. (2000) Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta. Proc Natl Acad Sci USA, 97 (6): 2603-8. [PMID:10706604]

Mohebiany AN, Nikolaienko RM, Bouyain S, Harroch S. (2013) Receptor-type tyrosine phosphatase ligands: looking for the needle in the haystack. FEBS J, 280 (2): 388-400. [PMID:22682003]

* Papadimitriou E, Pantazaka E, Castana P, Tsalios T, Polyzos A, Beis D. (2016) Pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta as regulators of angiogenesis and cancer. Biochim Biophys Acta, 1866 (2): 252-265. [PMID:27693125]

Sastry SK, Elferink LA. (2011) Checks and balances: interplay of RTKs and PTPs in cancer progression. Biochem Pharmacol, 82 (5): 435-40. [PMID:21704606]

Schmitt I, Bitoun E, Manto M. (2009) PTPRR, cerebellum, and motor coordination. Cerebellum, 8 (2): 71-3. [PMID:19488825]

Shen Y, Tenney AP, Busch SA, Horn KP, Cuascut FX, Liu K, He Z, Silver J, Flanagan JG. (2009) PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science, 326 (5952): 592-6. [PMID:19833921]

* Stanford SM, Bottini N. (2017) Targeting Tyrosine Phosphatases: Time to End the Stigma. Trends Pharmacol Sci, 38 (6): 524-540. [PMID:28412041]

Torii S. (2009) Expression and function of IA-2 family proteins, unique neuroendocrine-specific protein-tyrosine phosphatases. Endocr J, 56 (5): 639-48. [PMID:19550073]

Vang T, Miletic AV, Arimura Y, Tautz L, Rickert RC, Mustelin T. (2008) Protein tyrosine phosphatases in autoimmunity. Annu Rev Immunol, 26: 29-55. [PMID:18303998]

Walzel H, Schulz U, Neels P, Brock J. (1999) Galectin-1, a natural ligand for the receptor-type protein tyrosine phosphatase CD45. Immunol Lett, 67 (3): 193-202. [PMID:10369126]

1. Bouyain S, Watkins DJ. (2010) The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules. Proc Natl Acad Sci USA, 107 (6): 2443-8. [PMID:20133774]

2. Haftchenary S, Ball DP, Aubry I, Landry M, Shahani VM, Fletcher S, Page BDG, Jouk AO, Tremblay ML, Gunning PT. (2013) Identification of a potent salicylic acid-based inhibitor of tyrosine phosphatase PTP1B. Medchemcomm, (4): 987-992.

3. He Y, Liu S, Menon A, Stanford S, Oppong E, Gunawan AM, Wu L, Wu DJ, Barrios AM, Bottini N et al.. (2013) A potent and selective small-molecule inhibitor for the lymphoid-specific tyrosine phosphatase (LYP), a target associated with autoimmune diseases. J Med Chem, 56 (12): 4990-5008. [PMID:23713581]

4. Kim YS, Jung JA, Kim HJ, Ahn YH, Yoo JS, Oh S, Cho C, Yoo HS, Ko JH. (2011) 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, 404 (1): 96-102. [PMID:21094132]

5. Kwon SK, Woo J, Kim SY, Kim H, Kim E. (2010) Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma via specific domains regulate excitatory synapse formation. J Biol Chem, 285 (18): 13966-78. [PMID:20139422]

6. Li H, Zhang P, Liu C, Wang Y, Deng Y, Dong W, Yu Y. (2022) The Structure, Function and Regulation of Protein Tyrosine Phosphatase Receptor Type J and Its Role in Diseases. Cells, 12 (1). [PMID:36611803]

7. Ling Q, Huang Y, Zhou Y, Cai Z, Xiong B, Zhang Y, Ma L, Wang X, Li X, Li J et al.. (2008) Illudalic acid as a potential LAR inhibitor: synthesis, SAR, and preliminary studies on the mechanism of action. Bioorg Med Chem, 16 (15): 7399-409. [PMID:18579388]

8. Meng K, Rodriguez-Peña A, Dimitrov T, Chen W, Yamin M, Noda M, Deuel TF. (2000) Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta. Proc Natl Acad Sci USA, 97 (6): 2603-8. [PMID:10706604]

9. Shen Y, Tenney AP, Busch SA, Horn KP, Cuascut FX, Liu K, He Z, Silver J, Flanagan JG. (2009) PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science, 326 (5952): 592-6. [PMID:19833921]

10. Sheriff S, Beno BR, Zhai W, Kostich WA, McDonnell PA, Kish K, Goldfarb V, Gao M, Kiefer SE, Yanchunas J et al.. (2011) Small molecule receptor protein tyrosine phosphatase γ (RPTPγ) ligands that inhibit phosphatase activity via perturbation of the tryptophan-proline-aspartate (WPD) loop. J Med Chem, 54 (19): 6548-62. [PMID:21882820]

11. Uguccioni M, Mackay CR, Ochensberger B, Loetscher P, Rhis S, LaRosa GJ, Rao P, Ponath PD, Baggiolini M, Dahinden CA. (1997) High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines. J Clin Invest, 100 (5): 1137-43. [PMID:9276730]

12. Walzel H, Schulz U, Neels P, Brock J. (1999) Galectin-1, a natural ligand for the receptor-type protein tyrosine phosphatase CD45. Immunol Lett, 67 (3): 193-202. [PMID:10369126]

Chloe J. Peach Division of Physiology, Pharmacology & Neuroscience School of Life Sciences, Centre of Membrane Proteins and Receptors (COMPARE) University of Nottingham Medical School Nottingham NG7 2UH UK