| Author | Search for: Bivona, T.; Search for: Quatela, S.; Search for: Bodemann, B.; Search for: Ahearn, I.; Search for: Soskis, M.; Search for: Mor, A.; Search for: Miura, J.; Search for: Wiener, H.; Search for: Wright, L.; Search for: Saba, S.; Search for: Yim, D.; Search for: Fein, A.; Search for: Castro,I., Perez, De; Search for: Li, Chun; Search for: Thompson, C.; Search for: Cox, A.; Search for: Philips, M. |
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| Format | Text, Article |
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| Subject | cell; Cells; In Vitro; Location; membrane; Membranes; Mitochondria; Pathway; Phosphorylation; plasma; protein; Region; Sequence |
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| Abstract | 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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| Publication date | 2006-02-17 |
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| In | |
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| Language | English |
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| NRC number | BIVONA2006 |
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| NPARC number | 9389260 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 9dc39992-7048-449a-9f71-94e3d888020f |
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| Record created | 2009-07-10 |
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| Record modified | 2020-04-22 |
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