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Role of Protein Tyrosine Phosphatases in Signaling and Emerging Therapeutic Strategies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Role of Xenobiotics".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 19371

Special Issue Editors

Prof. Dr. Gonzalo Herradon

E-Mail Website
Guest Editor
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Alcorcón, 28925 Madrid, Spain
Interests: aging; neurodegeneration; neuroinflammation; addiction; drug discovery
Prof. Dr. Marta Vicente-Rodríguez

E-Mail Website
Guest Editor
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Alcorcón, 28925 Madrid, Spain
Interests: neuroinflammation; neurodegeneration; neuropharmacology; microglia; neuroimaging

Special Issue Information

Dear Colleagues,

During the last few decades, protein tyrosine phosphatases (PTPs) have gained increasing attention as we came to understand the key role of tyrosine phosphorylation in intracellular signaling. However, the specificity of protein phosphatases and many of their crucial functions in the regulation of signal transduction remain to be elucidated.

Since the balanced activity of PTPs and protein tyrosine kinases (PTKs) is essential for the regulation of tyrosine phosphorylation at the level of the whole organism, the disruption of this balance underlies a wide variety of diseases. Thus, the interest in PTPs (including the receptor-like class) as main targets for drug design is rapidly increasing in areas like metabolic disorders, cancer, neurodegenerative diseases, and neuropsychiatric disorders.

This Special Issue aims to highlight the molecular mechanisms regulated by PTPs in health and disease, with a focus on emerging therapeutic targets. Both original research articles and reviews are welcome.

Prof. Dr. Gonzalo Herradon
Prof. Dr. Marta Vicente-Rodríguez
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • signal transduction
  • phosphorylation
  • PTP
  • RPTP
  • targets
  • signaling pathways
  • dephosphorylation

Published Papers (5 papers)

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Research

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11 pages, 1837 KiB  
Communication
Role of Receptor Protein Tyrosine Phosphatase β/ζ in Neuron–Microglia Communication in a Cellular Model of Parkinson’s Disease
by Marta del Campo, Rosalía Fernández-Calle, Marta Vicente-Rodríguez, Sara Martín Martínez, Esther Gramage, José María Zapico, María Haro and Gonzalo Herradon
Int. J. Mol. Sci. 2021, 22(13), 6646; https://doi.org/10.3390/ijms22136646 - 22 Jun 2021
Cited by 5 | Viewed by 2653
Abstract
Pleiotrophin (PTN) is a neurotrophic factor that regulates glial responses in animal models of different types of central nervous system (CNS) injuries. PTN is upregulated in the brain in different pathologies characterized by exacerbated neuroinflammation, including Parkinson’s disease. PTN is an endogenous inhibitor [...] Read more.
Pleiotrophin (PTN) is a neurotrophic factor that regulates glial responses in animal models of different types of central nervous system (CNS) injuries. PTN is upregulated in the brain in different pathologies characterized by exacerbated neuroinflammation, including Parkinson’s disease. PTN is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ, which is abundantly expressed in the CNS. Using a specific inhibitor of RPTPβ/ζ (MY10), we aimed to assess whether the PTN/RPTPβ/ζ axis is involved in neuronal and glial injury induced by the toxin MPP+. Treatment with the RPTPβ/ζ inhibitor MY10 alone decreased the viability of both SH-SY5Y neuroblastoma cells and BV2 microglial cultures, suggesting that normal RPTPβ/ζ function is involved in neuronal and microglial viability. We observed that PTN partially decreased the cytotoxicity induced by MPP+ in SH-SY5Y cells underpinning the neuroprotective function of PTN. However, MY10 did not seem to modulate the SH-SY5Y cell loss induced by MPP+. Interestingly, we observed that media from SH-SY5Y cells treated with MPP+ and MY10 decreases microglial viability but may elicit a neuroprotective response of microglia by upregulating Ptn expression. The data suggest a neurotrophic role of microglia in response to neuronal injury through upregulation of Ptn levels. Full article
(This article belongs to the Special Issue Role of Protein Tyrosine Phosphatases in Signaling and Emerging Therapeutic Strategies)
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Review

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19 pages, 1882 KiB  
Review
Protein Tyrosine Phosphatases: Mechanisms in Cancer
by Vignesh Sivaganesh, Varsha Sivaganesh, Christina Scanlon, Alexander Iskander, Salma Maher, Thư Lê and Bela Peethambaran
Int. J. Mol. Sci. 2021, 22(23), 12865; https://doi.org/10.3390/ijms222312865 - 28 Nov 2021
Cited by 23 | Viewed by 5761
Abstract
Protein tyrosine kinases, especially receptor tyrosine kinases, have dominated the cancer therapeutics sphere as proteins that can be inhibited to selectively target cancer. However, protein tyrosine phosphatases (PTPs) are also an emerging target. Though historically known as negative regulators of the oncogenic tyrosine [...] Read more.
Protein tyrosine kinases, especially receptor tyrosine kinases, have dominated the cancer therapeutics sphere as proteins that can be inhibited to selectively target cancer. However, protein tyrosine phosphatases (PTPs) are also an emerging target. Though historically known as negative regulators of the oncogenic tyrosine kinases, PTPs are now known to be both tumor-suppressive and oncogenic. This review will highlight key protein tyrosine phosphatases that have been thoroughly investigated in various cancers. Furthermore, the different mechanisms underlying pro-cancerous and anti-cancerous PTPs will also be explored. Full article
(This article belongs to the Special Issue Role of Protein Tyrosine Phosphatases in Signaling and Emerging Therapeutic Strategies)
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21 pages, 2663 KiB  
Review
The Roles of Pseudophosphatases in Disease
by Andrew M. Mattei, Jonathan D. Smailys, Emma Marie Wilber Hepworth and Shantá D. Hinton
Int. J. Mol. Sci. 2021, 22(13), 6924; https://doi.org/10.3390/ijms22136924 - 28 Jun 2021
Cited by 12 | Viewed by 2967
Abstract
The pseudophosphatases, atypical members of the protein tyrosine phosphatase family, have emerged as bona fide signaling regulators within the past two decades. Their roles as regulators have led to a renaissance of the pseudophosphatase and pseudoenyme fields, catapulting interest from a mere curiosity [...] Read more.
The pseudophosphatases, atypical members of the protein tyrosine phosphatase family, have emerged as bona fide signaling regulators within the past two decades. Their roles as regulators have led to a renaissance of the pseudophosphatase and pseudoenyme fields, catapulting interest from a mere curiosity to intriguing and relevant proteins to investigate. Pseudophosphatases make up approximately fourteen percent of the phosphatase family, and are conserved throughout evolution. Pseudophosphatases, along with pseudokinases, are important players in physiology and pathophysiology. These atypical members of the protein tyrosine phosphatase and protein tyrosine kinase superfamily, respectively, are rendered catalytically inactive through mutations within their catalytic active signature motif and/or other important domains required for catalysis. This new interest in the pursuit of the relevant functions of these proteins has resulted in an elucidation of their roles in signaling cascades and diseases. There is a rapid accumulation of knowledge of diseases linked to their dysregulation, such as neuropathies and various cancers. This review analyzes the involvement of pseudophosphatases in diseases, highlighting the function of various role(s) of pseudophosphatases involvement in pathologies, and thus providing a platform to strongly consider them as key therapeutic drug targets. Full article
(This article belongs to the Special Issue Role of Protein Tyrosine Phosphatases in Signaling and Emerging Therapeutic Strategies)
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11 pages, 1195 KiB  
Review
Role of Receptor Protein Tyrosine Phosphatases (RPTPs) in Insulin Signaling and Secretion
by Julio Sevillano, María Gracia Sánchez-Alonso, Javier Pizarro-Delgado and María del Pilar Ramos-Álvarez
Int. J. Mol. Sci. 2021, 22(11), 5812; https://doi.org/10.3390/ijms22115812 - 28 May 2021
Cited by 16 | Viewed by 4496
Abstract
Changes in lifestyle in developed countries have triggered the prevalence of obesity and type 2 diabetes mellitus (T2DM) in the latest years. Consequently, these metabolic diseases associated to insulin resistance, and the morbidity associated with them, accounts for enormous costs for the health [...] Read more.
Changes in lifestyle in developed countries have triggered the prevalence of obesity and type 2 diabetes mellitus (T2DM) in the latest years. Consequently, these metabolic diseases associated to insulin resistance, and the morbidity associated with them, accounts for enormous costs for the health systems. The best way to face this problem is to identify potential therapeutic targets and/or early biomarkers to help in the treatment and in the early detection. In the insulin receptor signaling cascade, the activities of protein tyrosine kinases and phosphatases are coordinated, thus, protein tyrosine kinases amplify the insulin signaling response, whereas phosphatases are required for the regulation of the rate and duration of that response. The focus of this review is to summarize the impact of transmembrane receptor protein tyrosine phosphatase (RPTPs) in the insulin signaling cascade and secretion, and their implication in metabolic diseases such as obesity and T2DM. Full article
(This article belongs to the Special Issue Role of Protein Tyrosine Phosphatases in Signaling and Emerging Therapeutic Strategies)
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14 pages, 2106 KiB  
Review
Type IIa RPTPs and Glycans: Roles in Axon Regeneration and Synaptogenesis
by Kazuma Sakamoto, Tomoya Ozaki, Yuji Suzuki and Kenji Kadomatsu
Int. J. Mol. Sci. 2021, 22(11), 5524; https://doi.org/10.3390/ijms22115524 - 24 May 2021
Cited by 10 | Viewed by 2768
Abstract
Type IIa receptor tyrosine phosphatases (RPTPs) play pivotal roles in neuronal network formation. It is emerging that the interactions of RPTPs with glycans, i.e., chondroitin sulfate (CS) and heparan sulfate (HS), are critical for their functions. We highlight here the significance of these [...] Read more.
Type IIa receptor tyrosine phosphatases (RPTPs) play pivotal roles in neuronal network formation. It is emerging that the interactions of RPTPs with glycans, i.e., chondroitin sulfate (CS) and heparan sulfate (HS), are critical for their functions. We highlight here the significance of these interactions in axon regeneration and synaptogenesis. For example, PTPσ, a member of type IIa RPTPs, on axon terminals is monomerized and activated by the extracellular CS deposited in neural injuries, dephosphorylates cortactin, disrupts autophagy flux, and consequently inhibits axon regeneration. In contrast, HS induces PTPσ oligomerization, suppresses PTPσ phosphatase activity, and promotes axon regeneration. PTPσ also serves as an organizer of excitatory synapses. PTPσ and neurexin bind one another on presynapses and further bind to postsynaptic leucine-rich repeat transmembrane protein 4 (LRRTM4). Neurexin is now known as a heparan sulfate proteoglycan (HSPG), and its HS is essential for the binding between these three molecules. Another HSPG, glypican 4, binds to presynaptic PTPσ and postsynaptic LRRTM4 in an HS-dependent manner. Type IIa RPTPs are also involved in the formation of excitatory and inhibitory synapses by heterophilic binding to a variety of postsynaptic partners. We also discuss the important issue of possible mechanisms coordinating axon extension and synapse formation. Full article
(This article belongs to the Special Issue Role of Protein Tyrosine Phosphatases in Signaling and Emerging Therapeutic Strategies)
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