RET Protein, Human (HEK293, His)

The RET protein, a receptor tyrosine-protein kinase, plays a crucial role in diverse cellular processes such as cell proliferation, neuronal navigation, migration, and differentiation upon binding with glial cell-derived neurotrophic factor family ligands. It phosphorylates PTK2/FAK1 and regulates the delicate balance between cell death and survival, as well as positional information. Essential for the molecular coordination during intestine organogenesis, RET is involved in the development of the enteric nervous system, renal organogenesis, and promotes the formation of Peyer's patch-like structures in the gut-associated lymphoid tissue. Furthermore, RET modulates cell adhesion, mediated by caspase cleavage in sympathetic neurons, and facilitates cell migration in an integrin-dependent manner. Operating as a dependence receptor, it triggers apoptosis in the absence of the ligand GDNF in somatotrophs but promotes survival and downregulates growth hormone production in its presence. RET is a key mediator in various diseases, particularly neuroendocrine cancers characterized by aberrant integrins-regulated cell migration. Additionally, it mediates GDF15-induced cell signaling in the brainstem through interaction with GFRAL, resulting in the inhibition of food intake and activation of MAPK- and AKT-signaling pathways. Notably, isoform 1 in complex with GFRAL induces higher activation of the MAPK-signaling pathway compared to isoform 2 in the same complex.