Negative regulation of receptor tyrosine kinases by ubiquitination: Key roles of the Cbl family of E3 ubiquitin ligases

Rong Tang; Wallace Y. Langdon; Jian Zhang

doi:10.3389/fendo.2022.971162

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Negative regulation of receptor tyrosine kinases by ubiquitination: Key roles of the Cbl family of E3 ubiquitin ligases

Journal article

Open access

Peer reviewed

Negative regulation of receptor tyrosine kinases by ubiquitination: Key roles of the Cbl family of E3 ubiquitin ligases

Rong Tang, Wallace Y. Langdon and Jian Zhang

Frontiers in endocrinology, Vol.13, 971162

07/01/2022

DOI: 10.3389/fendo.2022.971162

PMCID: PMC9365936

PMID: 35966060

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Abstract

Receptor tyrosine kinases (RTKs) serve as transmembrane receptors that participate in a broad spectrum of cellular processes including cellular growth, motility, differentiation, proliferation, and metabolism. Hence, elucidating the regulatory mechanisms of RTKs involved in an assortment of diseases such as cancers attracts increasing interest from researchers. Members of the Cbl family ubiquitin ligases (c-Cbl, Cbl-b and Cbl-c in mammals) have emerged as negative regulators of activated RTKs. Upon activation of RTKs by growth factors, Cbl binds to RTKs via its tyrosine kinase binding (TKB) domain and targets them for ubiquitination, thus facilitating their degradation and negative regulation of RTK signaling. RTKs such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGF), fibroblast growth factor receptor (FGFR) and hepatocyte growth factor receptor (HGFR) undergo ubiquitination upon interaction with Cbl family members. In this review, we summarize the current knowledge related to the negative regulation of RTKs by Cbl family proteins.

cbl

degradation

negative regulation

receptor tyrosine kinases

ubiquitination

Details

Title: Subtitle: Negative regulation of receptor tyrosine kinases by ubiquitination: Key roles of the Cbl family of E3 ubiquitin ligases
Creators: Rong Tang - Xiangya Hospital Central South University
Wallace Y. Langdon - The University of Western Australia
Jian Zhang - University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in endocrinology, Vol.13, 971162
DOI: 10.3389/fendo.2022.971162
PMID: 35966060
PMCID: PMC9365936
NLM abbreviation: Front Endocrinol (Lausanne)
ISSN: 1664-2392
Publisher: Frontiers Media S.A
Language: English
Date published: 07/01/2022
Academic Unit: Pathology
Record Identifier: 9984279258102771

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