Rearranged during Transfection Receptor Tyrosine Kinase (RET)

RET (Rearranged during Transfection) is a receptor tyrosine kinase crucial for cell proliferation, differentiation, survival, migration, and metabolism. It is essential for the development of the nervous system. RET is activated upon binding of GDNF family ligands to GFRα co-receptors, leading to receptor dimerization and autophosphorylation, activating downstream signaling pathways like MAPK/ERK, PI3K/AKT, and JAK/STAT. Mutations and aberrant activation of RET are implicated in various cancers, including thyroid cancers, and Hirschsprung disease. Therapeutic targeting includes small-molecule inhibitors for cancer therapy, with ongoing interest in agonists for neurodegenerative conditions.

Other names

RET proto-oncogeneProto-oncogene c-RetCDHF12MEN2AMEN2BMTC1PTC2RET51Multiple endocrine neoplasia type 2

Small molecule inhibitors bind to the ATP-binding pocket of the RET kinase domain, preventing autophosphorylation and downstream signaling.