Auteur | Rechercher : Bivona, T.; Rechercher : Quatela, S.; Rechercher : Bodemann, B.; Rechercher : Ahearn, I.; Rechercher : Soskis, M.; Rechercher : Mor, A.; Rechercher : Miura, J.; Rechercher : Wiener, H.; Rechercher : Wright, L.; Rechercher : Saba, S.; Rechercher : Yim, D.; Rechercher : Fein, A.; Rechercher : Castro,I., Perez, De; Rechercher : Li, Chun; Rechercher : Thompson, C.; Rechercher : Cox, A.; Rechercher : Philips, M. |
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Format | Texte, Article |
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Sujet | cell; Cells; In Vitro; Location; membrane; Membranes; Mitochondria; Pathway; Phosphorylation; plasma; protein; Region; Sequence |
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Résumé | K-Ras associates with the plasma membrane (PM) through farnesylation that functions in conjunction with an adjacent polybasic sequence. We show that phosphorylation by protein kinase C (PKC) of S181 within the polybasic region promotes rapid dissociation of K-Ras from the PM and association with intracellular membranes, including the outer membrane of mitochondria where phospho-K-Ras interacts with Bcl-Xl. PKC agonists promote apoptosis of cells transformed with oncogenic K-Ras in a S181-dependent manner. K-Ras with a phosphomimetic residue at position 181 induces apoptosis via a pathway that requires Bcl-Xl. The PKC agonist bryostatin-1 inhibited the growth in vitro and in vivo of cells transformed with oncogenic K-Ras in a S181-dependent fashion. These data demonstrate that the location and function of K-Ras are regulated directly by PKC and suggest an approach to therapy of K-Ras-dependent tumors with agents that stimulate phosphorylation of S181 |
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Date de publication | 2006-02-17 |
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Dans | |
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Langue | anglais |
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Numéro du CNRC | BIVONA2006 |
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Numéro NPARC | 9389260 |
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Exporter la notice | Exporter en format RIS |
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Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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Identificateur de l’enregistrement | 9dc39992-7048-449a-9f71-94e3d888020f |
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Enregistrement créé | 2009-07-10 |
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Enregistrement modifié | 2020-04-22 |
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