Taxol-induced Apoptosis and Phosphorylation of Bcl-2 Protein Involves c-Raf-1 and Represents a Novel c-Raf-1 Signal Transduction Pathway

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阅读量:

80

作者:

MV BlagosklonnyTW SchulteP NguyenJ TrepelLM Neckers

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摘要:

c-Raf-1 (Raf-1) is a central component of signal transduction pathways stimulated by various growth factors, protein kinase C, and other protein kinases. Raf-1 activation is thought to be initiated at the plasma membrane after its recruitment by Ras. Raf-1 activation is associated primarily with proliferation and cell survival, but it has also been implicated in apoptosis. Raf-1 has also been shown to form complexes with both R-Ras and Bcl-2, raising the possibility that this component of cellular Raf-1 plays a role in apoptosis. Recently, taxol was reported to induce Bcl-2 phosphorylation and inactivation. We have previously demonstrated Raf-1 activation following taxol in MCF7 cells. We now present evidence that taxol fails to stimulate either apoptosis or phosphorylation of Bel-2 in the absence of Raf-1. Moreover, Raf-1 activation by taxol coincided with Bel-2 phosphorylation, showing similar dose and time dependence. Thus, our data support a role for a distinct subcellular component of Raf-1, which is taxol but not phorbol myristate acetate sensitive, in mediating an apoptotic pathway involving Bc1-2.

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DOI:

doi:10.1002/(SICI)1097-0142(19960415)77:8+<1752::AID-CNCR27>3.0.

被引量:

839

年份:

1996

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来源期刊

Cancer Research
1996-04-15

引用走势

1999
被引量:83

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