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Anti-apoptotic Signaling of the Insulin-like Growth Factor-I Receptor through Mitochondrial Translocation of c-Raf and Nedd4
Peruzzi, Francesca Prisco, Marco Valentinis, Barbara Baserga, Renato
Peruzzi, Francesca
Prisco, Marco
Valentinis, Barbara
Baserga, Renato
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Journal article
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2001-07-13
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Biology
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https://doi.org/10.1074/jbc.M103188200
Abstract
The type 1 insulin-like growth factor receptor (IGF-IR) sends a strong anti-apoptotic signal by at least three different pathways. By using mutants of the IGF-IR, we showed that one of the pathways depends on residues of the IGF-IR (serines 1280–1283) that interact with 14.3.3 proteins. The result is the activation of Raf-1 and the mitochondrial translocation of both Raf-1 and Nedd4, a target of caspases. A mutant IGF-IR in which the serines at positions 1280–1283 have been mutated to alanine does not protect from apoptosis and fails to translocate Nedd4 or Raf-1 to the mitochondria. This failure is accompanied by a loss of cytochrome c from the mitochondria. The 14.3.3/Raf-1/Nedd4 pathway is operative in the presence or absence of the insulin receptor substrate-1.
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Francesca Peruzzi, Marco Prisco, Andrea Morrione, Barbara Valentinis, Renato Baserga, Anti-apoptotic Signaling of the Insulin-like Growth Factor-I Receptor through Mitochondrial Translocation of c-Raf and Nedd4, Journal of Biological Chemistry, Volume 276, Issue 28, 2001, Pages 25990-25996, ISSN 0021-9258, https://doi.org/10.1074/jbc.M103188200.
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Elsevier
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Journal of Biological Chemistry, Vol. 276, No. 28
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