The oncogenic tyrosine kinase Lyn impairs the pro-apoptotic function of Bim.

Abstract : Phosphorylation of Ser/Thr residues is a well-established modulating mechanism of the pro-apoptotic function of the BH3-only protein Bim. However, nothing is known about the putative tyrosine of this Bcl-2 family member and its potential impact on Bim function and subsequent Bax/Bak-mediated cytochrome c release and apoptosis. As we have previously shown that the tyrosine kinase Lyn could behave as an anti-apoptic molecule, we investigated whether this Src family member could directly regulate the pro-apoptotic function of Bim. In the present study, we show that Bim is phosphorylated onto tyrosine residues 92 and 161 by Lin, which results is an inhibition of its pro-apoptotic function. Mechanistically, we show that Lyn-dependent tyrosine phosphorylation of Bim increases its interaction with anti-apoptic members such as Bcl-xL, therefore limiting mitochondrial outer membrane permeabilization and subsequent apoptosis. Collectively, our data uncover one molecular mechanism through which the oncogenic tyrosine kinase Lyn negatively regulates the mitochondrial apoptic pathway, which may contribute to the transformation and/or the chemotherapeutic resistance of cancer cells.
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https://www.hal.inserm.fr/inserm-01814383
Contributor : Elizabeth Bernardo <>
Submitted on : Wednesday, June 13, 2018 - 11:18:05 AM
Last modification on : Monday, May 20, 2019 - 3:32:02 PM

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Lazaro Aira, Elodie Villa, Pascal Colosetti, Parvati Gamas, Laurie Signetti, et al.. The oncogenic tyrosine kinase Lyn impairs the pro-apoptotic function of Bim.. Oncogene, Nature Publishing Group, 2018, 37 (16), pp.2122 - 2136. ⟨10.1038/s41388-017-0112-0⟩. ⟨inserm-01814383⟩

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