Functional impact of PTP1B-mediated Src regulation on oxidative phosphorylation in rat brain mitochondria |
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Authors: | Email author" target="_blank">Etienne?Hébert ChatelainEmail author Jean-William?Dupuy Thierry?Letellier Jeanne?Dachary-Prigent |
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Institution: | 1.Physiopathologie Mitochondriale,INSERM-U688, Université Victor Ségalen-Bordeaux 2,Bordeaux-Cedex,France;2.P?le Protéomique, Centre de Génomique Fonctionnelle,Université de Bordeaux,Bordeaux,France |
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Abstract: | Given the presence of Src and PTP1B within rat brain mitochondria, we have investigated whether PTP1B regulates Src activity
in mitochondria as in the cytosol. Results showed that Src was stimulated by in vitro addition of ATP to mitochondria, and
this stimulation was reversed by a membrane-permeable allosteric inhibitor of PTP1B and by a potent selective Src inhibitor.
They also indicated a direct action of PTP1B on phosphorylated tyrosine 527 residue of Src, thus implicating a role for PTP1B
in the modulation of Src activity in mitochondria. Putative Src and PTP1B substrates were identified by liquid chromatography
tandem mass spectrometry and two-dimensional blue native/SDS-PAGE. Both inhibitors inhibited ADP-stimulated respirations concurrently
with Src activation and complex IV activation by ATP, while having no effect or increasing the activity of the other complexes.
Our analysis emphasizes the regulatory function of Src and its modulation by PTP1B on oxidative phosphorylation in mitochondria. |
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