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

MARGIOTTA, Azzurra. All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal. International Journal of Molecular Sciences. Basel: MDPI, 2021, vol. 22, No 12, p. 1-14. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms22126342.

Basic information

• Original name: All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal
• Authors: MARGIOTTA, Azzurra (380 Italy, guarantor, belonging to the institution).
• Edition: International Journal of Molecular Sciences, Basel, MDPI, 2021, 1422-0067.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: Switzerland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 6.208
• RIV identification code: RIV/00216224:14110/21:00124195
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.3390/ijms22126342
• UT WoS: 000665932000001
• Keywords in English: RTKs; FGFRs; termination of signaling; degradation; ubiquitination; PTPs; kinases
• Tags: 14110513, rivok
• Tags: International impact, Reviewed

Abstract

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.