Tyrosine-protein kinase RET (RET)

Tyrosine-protein kinase RET (RET) is a receptor tyrosine kinase encoded by the RET proto-oncogene, primarily expressed as a cell-surface protein with extracellular cadherin-like domains and a cytoplasmic kinase domain. RET is activated by ligands of the glial cell line-derived neurotrophic factor (GDNF) family, which require GFRα co-receptors for RET binding and function. Ligand binding induces RET dimerization and autophosphorylation, initiating intracellular signaling cascades (MAPK, PI3K, and PLCγ pathways) critical for kidney and enteric nervous system development. Loss-of-function RET mutations cause Hirschsprung’s disease, while gain-of-function mutations, fusions, or rearrangements are oncogenic, driving cancers such as papillary thyroid carcinoma, multiple endocrine neoplasias, and certain lung cancers. Selective and multikinase RET inhibitors are approved or in development for cancer therapy, with patient selection guided by RET mutation or fusion status[1][2].

Other names

RET proto-oncogeneRearranged during transfectionRET receptorRET tyrosine kinase

Kinase inhibition: Drugs bind to the active site of RET, inhibiting its tyrosine kinase activity and thereby blocking downstream signaling that promotes cell proliferation and survival. Targeting fusions or mutations: Some drugs are selective for RET mutations or RET fusion proteins in cancer.