Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2022.133
Caspase Cleavage of Receptor Tyrosine Kinases in the Dependence Receptor Family
Gyu Hwan Park1,†, Yoo Kyung Kang2,†, Seung-Mann Paek2, Chan Young Shin3 and Sun-Young Han2,*
1College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566,
2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju 52828,
3Department of Neuroscience and Pharmacology, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea
*E-mail: syhan@gnu.ac.kr
Tel: +82-55-772-2423, Fax: +82-55-772-2429
†The first two authors contributed equally to this work.
Received: October 24, 2022; Revised: January 19, 2023; Accepted: February 14, 2023; Published online: March 15, 2023.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Dependence receptors are a group of receptor proteins with shared characteristics of transducing two different signals within cells. They can transduce a positive signal of survival and differentiation in the presence of ligands. On the other hand, dependence receptors can transduce an apoptosis signal in the absence of ligands. The function of these receptors depends on the availability of their ligands. Several receptor tyrosine kinases (RTKs) have been reported as dependence receptors. When cells undergo apoptosis by dependence receptors, the intracellular domain of some RTKs is cleaved by the caspases. Among the RTKs that belong to dependence receptors, we focused on eight RTKs (RET, HER2, MET, ALK, TrkC, EphA4, EphB3, and c-KIT) that are cleaved by caspases. In this review, we describe the features of the receptors, their cleavage sites, and the fate of the cleaved products, as well as recent implications on them being used as potential therapeutics for cancer treatment.
Keywords: Dependence receptor, Cleavage, Receptor tyrosine kinase, Caspase

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