Targeting Receptor-Type Protein Tyrosine Phosphatases with Biotherapeutics: Is Outside-in Better than Inside-Out?

Senis, Y. A. and Barr, A.J. 2018. Targeting Receptor-Type Protein Tyrosine Phosphatases with Biotherapeutics: Is Outside-in Better than Inside-Out? Molecules. 23 (3), pp. 569-585. doi:10.3390/molecules23030569

TitleTargeting Receptor-Type Protein Tyrosine Phosphatases with Biotherapeutics: Is Outside-in Better than Inside-Out?
AuthorsSenis, Y. A. and Barr, A.J.
Abstract

Protein tyrosine phosphatases (PTPs), of the receptor and non-receptor classes, are key signaling molecules that play critical roles in cellular regulation underlying diverse physiological events. Aberrant signaling as a result of genetic mutation or altered expression levels has been associated with several diseases and treatment via pharmacological intervention at the level of PTPs has been widely explored; however, the challenges associated with development of small molecule phosphatase inhibitors targeting the intracellular phosphatase domain (the “inside-out” approach) have been well documented and as yet there are no clinically approved drugs targeting these enzymes. The alternative approach of targeting receptor PTPs with biotherapeutic agents (such as monoclonal antibodies or engineered fusion proteins; the “outside-in” approach) that interact with the extracellular ectodomain offers many advantages, and there have been a number of exciting recent developments in this field. Here we provide a brief overview of the receptor PTP family and an update on the emerging area of receptor PTP-targeted biotherapeutics for CD148, vascular endothelial-protein tyrosine phosphatase (VE-PTP), receptor-type PTPs σ, γ, ζ (RPTPσ, RPTPγ, RPTPζ) and CD45, and discussion of future potential in this area.

Keywords tyrosine phosphatase; receptor; phosphorylation; ectodomain; biotherapeutic; biological; inhibitor; disease
Article number569
JournalMolecules
Journal citation23 (3), pp. 569-585
ISSN1420-3049
Year2018
PublisherMDPI
Publisher's versionSenis & Barr_molecules-23-00569.pdf
Digital Object Identifier (DOI)doi:10.3390/molecules23030569
Web address (URL)http://www.mdpi.com/1420-3049/23/3/569/htm
Publication dates
Published02 Mar 2018
LicenseCC BY 4.0

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