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FP5

GDNF Report Summary

Project ID: QLG3-CT-2002-01000
Funded under: FP5-LIFE QUALITY
Country: Finland

GDNF promotes tubulogenesis of GFR-1-expressing MDCK cells by Src-mediated phosphorylation of MET receptor tyrosine kinase

We have identified the receptor tyrosine kinase Met –the receptor for hepatocyte growth factor (HGF)– as the p150 downstream signaling component for both RET-dependent and -independent GDNF signaling. We have found that GDNF can partially restore ureteric branching morphogenesis in RET-deficient mice with severe renal hypodysplasia. In MDCK cells expressing GFR?1 but no RET, GDNF stimulated branching but not chemotactic migration, whereas both branching and chemotaxis were promoted by GDNF in cells co-expressing RET and GFR?1, mimicking HGF/Met responses in wild-type MDCK cells. However, GDNF did not bind to Met, implicating the participation of an alternative GDNF binding subunit. Met activation was mediated by Src family kinases. The GDNF-induced branching of MDCK cells required Src activation, whereas the HGF-induced branching did not. These data reveal a mechanism for GDNF-induced branching morphogenesis that is not dependent on the RET receptor.

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Raija SOLLAMO
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