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RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer
Rearranged during transfection (RET) is the tyrosine kinase receptor that under normal circumstances interacts with ligand at the cell surface and mediates various essential roles in a variety of cellular processes such as proliferation, differentiation, survival, migration, and metabolism. RET play...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583994/ https://www.ncbi.nlm.nih.gov/pubmed/32993133 http://dx.doi.org/10.3390/ijms21197108 |
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author | Mahato, Arun Kumar Sidorova, Yulia A. |
author_facet | Mahato, Arun Kumar Sidorova, Yulia A. |
author_sort | Mahato, Arun Kumar |
collection | PubMed |
description | Rearranged during transfection (RET) is the tyrosine kinase receptor that under normal circumstances interacts with ligand at the cell surface and mediates various essential roles in a variety of cellular processes such as proliferation, differentiation, survival, migration, and metabolism. RET plays a pivotal role in the development of both peripheral and central nervous systems. RET is expressed from early stages of embryogenesis and remains expressed throughout all life stages. Mutations either activating or inhibiting RET result in several aggressive diseases, namely cancer and Hirschsprung disease. However, the physiological ligand-dependent activation of RET receptor is important for the survival and maintenance of several neuronal populations, appetite, and weight gain control, thus providing an opportunity for the development of disease-modifying therapeutics against neurodegeneration and obesity. In this review, we describe the structure of RET, its signaling, and its role in both normal conditions as well as in several disorders. We highlight the differences in the signaling and outcomes of constitutive and ligand-induced RET activation. Finally, we review the data on recently developed small molecular weight RET agonists and their potential for the treatment of various diseases. |
format | Online Article Text |
id | pubmed-7583994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75839942020-10-29 RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer Mahato, Arun Kumar Sidorova, Yulia A. Int J Mol Sci Review Rearranged during transfection (RET) is the tyrosine kinase receptor that under normal circumstances interacts with ligand at the cell surface and mediates various essential roles in a variety of cellular processes such as proliferation, differentiation, survival, migration, and metabolism. RET plays a pivotal role in the development of both peripheral and central nervous systems. RET is expressed from early stages of embryogenesis and remains expressed throughout all life stages. Mutations either activating or inhibiting RET result in several aggressive diseases, namely cancer and Hirschsprung disease. However, the physiological ligand-dependent activation of RET receptor is important for the survival and maintenance of several neuronal populations, appetite, and weight gain control, thus providing an opportunity for the development of disease-modifying therapeutics against neurodegeneration and obesity. In this review, we describe the structure of RET, its signaling, and its role in both normal conditions as well as in several disorders. We highlight the differences in the signaling and outcomes of constitutive and ligand-induced RET activation. Finally, we review the data on recently developed small molecular weight RET agonists and their potential for the treatment of various diseases. MDPI 2020-09-26 /pmc/articles/PMC7583994/ /pubmed/32993133 http://dx.doi.org/10.3390/ijms21197108 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Mahato, Arun Kumar Sidorova, Yulia A. RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer |
title | RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer |
title_full | RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer |
title_fullStr | RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer |
title_full_unstemmed | RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer |
title_short | RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer |
title_sort | ret receptor tyrosine kinase: role in neurodegeneration, obesity, and cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583994/ https://www.ncbi.nlm.nih.gov/pubmed/32993133 http://dx.doi.org/10.3390/ijms21197108 |
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