GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR ACTIVATES THE RECEPTOR TYROSINE KINASE RET AND PROMOTES KIDNEY MORPHOGENESIS

The receptor tyrosine kinase RET functions during the development of t he kidney and the enteric nervous system, yet no ligand has been ident ified to date, This report demonstrates that the glial cell line-deriv ed neurotrophic factor (GDNF) activates RET, as measured by tyrosine p hosphorylation of the intracellular catalytic domain, GDNF also binds RET with a dissociation constant of 8 nM, and I-125-labeled GDNF can b e coimmunoprecipitated with anti-RET antibodies, In addition, exogenou s GDNF stimulates both branching and proliferation of embryonic kidney s in organ culture, whereas neutralizing antibodies against GDNF inhib it branching morphogenesis, These data indicate that RET and GDNF are components of a common signaling pathway and point to a role for GDNF in kidney development.