Receptor tyrosine kinase RET (RET)

Receptor tyrosine kinase RET is a **transmembrane protein** encoded by the *RET* proto-oncogene. It functions as a receptor for glial cell line-derived neurotrophic factor family ligands (GFLs), which require co-receptors from the GDNF receptor-alpha family for activation. Upon ligand binding and complex formation at the cell surface, two molecules of RET dimerize and undergo autophosphorylation on specific intracellular tyrosine residues within their kinase domains. This phosphorylation event initiates multiple downstream signaling cascades regulating essential cellular processes such as proliferation, differentiation, migration, metabolism regulation, and neuronal survival. RET plays a critical role in embryonic development—especially of neural crest-derived tissues—and remains important throughout life for neuronal maintenance. Pathogenic gain-of-function mutations lead to various cancers including medullary thyroid carcinoma; loss-of-function mutations cause developmental diseases like Hirschsprung disease[1][4]. Selective inhibition of aberrant RET signaling has become an important therapeutic strategy in oncology. Key interacting proteins include DOK1/5, GDNF family receptor alpha subunits (GFRα1–4), GRB10/7/2 adaptor proteins, SHC1 adaptor protein, STAT3 transcription factor among others[1]. In summary: **Receptor tyrosine kinase RET** is a validated therapeutic target implicated in cancer biology as well as neurodevelopmental processes; it is targeted by several approved drugs based on its genetic status within tumors or other pathologies[1][4].

Other names

Rearranged during transfectionRET proto-oncogeneProto-oncogene c-RET

Drugs targeting RET typically act as small molecule inhibitors that block its intracellular tyrosine kinase activity, thereby inhibiting downstream signaling pathways involved in cell growth and survival. Some experimental agents may act as agonists to promote neurotrophic effects[4].