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All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal

Receptor tyrosine kinases (RTKs) are membrane receptors that regulate many fundamental cellular processes. A tight regulation of RTK signaling is fundamental for development and survival, and an altered signaling by RTKs can cause cancer. RTKs are localized at the plasma membrane (PM) and the major...

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Detalles Bibliográficos
Autor principal: Margiotta, Azzurra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231876/
https://www.ncbi.nlm.nih.gov/pubmed/34198477
http://dx.doi.org/10.3390/ijms22126342
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author Margiotta, Azzurra
author_facet Margiotta, Azzurra
author_sort Margiotta, Azzurra
collection PubMed
description Receptor tyrosine kinases (RTKs) are membrane receptors that regulate many fundamental cellular processes. A tight regulation of RTK signaling is fundamental for development and survival, and an altered signaling by RTKs can cause cancer. RTKs are localized at the plasma membrane (PM) and the major regulatory mechanism of signaling of RTKs is their endocytosis and degradation. In fact, RTKs at the cell surface bind ligands with their extracellular domain, become active, and are rapidly internalized where the temporal extent of signaling, attenuation, and downregulation are modulated. However, other mechanisms of signal attenuation and termination are known. Indeed, inhibition of RTKs’ activity may occur through the modulation of the phosphorylation state of RTKs and the interaction with specific proteins, whereas antagonist ligands can inhibit the biological responses mediated by the receptor. Another mechanism concerns the expression of endogenous inactive receptor variants that are deficient in RTK activity and take part to inactive heterodimers or hetero-oligomers. The downregulation of RTK signals is fundamental for several cellular functions and the homeostasis of the cell. Here, we will review the mechanisms of signal attenuation and termination of RTKs, focusing on FGFRs.
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spelling pubmed-82318762021-06-26 All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal Margiotta, Azzurra Int J Mol Sci Review Receptor tyrosine kinases (RTKs) are membrane receptors that regulate many fundamental cellular processes. A tight regulation of RTK signaling is fundamental for development and survival, and an altered signaling by RTKs can cause cancer. RTKs are localized at the plasma membrane (PM) and the major regulatory mechanism of signaling of RTKs is their endocytosis and degradation. In fact, RTKs at the cell surface bind ligands with their extracellular domain, become active, and are rapidly internalized where the temporal extent of signaling, attenuation, and downregulation are modulated. However, other mechanisms of signal attenuation and termination are known. Indeed, inhibition of RTKs’ activity may occur through the modulation of the phosphorylation state of RTKs and the interaction with specific proteins, whereas antagonist ligands can inhibit the biological responses mediated by the receptor. Another mechanism concerns the expression of endogenous inactive receptor variants that are deficient in RTK activity and take part to inactive heterodimers or hetero-oligomers. The downregulation of RTK signals is fundamental for several cellular functions and the homeostasis of the cell. Here, we will review the mechanisms of signal attenuation and termination of RTKs, focusing on FGFRs. MDPI 2021-06-14 /pmc/articles/PMC8231876/ /pubmed/34198477 http://dx.doi.org/10.3390/ijms22126342 Text en © 2021 by the author. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Margiotta, Azzurra
All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal
title All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal
title_full All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal
title_fullStr All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal
title_full_unstemmed All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal
title_short All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal
title_sort all good things must end: termination of receptor tyrosine kinase signal
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231876/
https://www.ncbi.nlm.nih.gov/pubmed/34198477
http://dx.doi.org/10.3390/ijms22126342
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