Caspase Cleavage of Receptor Tyrosine Kinases in the Dependence Receptor Family

Biomol Ther (Seoul). 2023 Jul 1;31(4):359-369. doi: 10.4062/biomolther.2022.133. Epub 2023 Mar 15.

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: Caspase; Cleavage; Dependence receptor; Receptor tyrosine kinase.

Publication types

  • Review

Grants and funding

ACKNOWLEDGMENTS This research was funded by the National Research Foundation, Government of Korea, grant number 2021R1A2C1007790 (S-Y.H.). The authors thank Ms. Jeong Min Lee for her illustrative work with the Figures.