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J Biol Chem. 2006 May 19;281(20):14330-9. Epub 2006 Mar 20.

Gas1 is related to the glial cell-derived neurotrophic factor family receptors alpha and regulates Ret signaling.

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Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Consejo Superior Investigaciones Cientificas, 28049 Madrid, Spain.


The growth arrest-specific gene 1 (Gas1) protein has been proposed to function during development as an inhibitor of growth and a mediator of cell death and is also re-expressed in adult neurons during excitotoxic insult. Here we have demonstrated that the Gas1 protein shows high structural similarity to the glial cell-derived neurotrophic factor (GDNF) family receptors alpha, which mediate GDNF responses through the receptor tyrosine kinase Ret. We found that Gas1 binds Ret in a ligand-independent manner and sequesters Ret in lipid rafts. Signaling downstream of Ret is thus modified through a mechanism that involves the adaptor protein Shc as well as ERK, eventually blocking Akt activation. Consequently, when Gas1 is induced, Ret-mediated GDNF-dependent survival effects are compromised.

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