TAXOL-INDUCED APOPTOSIS AND PHOSPHORYLATION OF BCL-2 PROTEIN INVOLVESC-RAF-1 AND REPRESENTS A NOVEL C-RAF-1 SIGNAL-TRANSDUCTION PATHWAY

c-Raf-l (Raf-l) is a central component of signal transduction pathways stimulated by various growth factors, protein kinase C, and other pro tein kinases. Raf-l activation is thought to be initiated at the plasm a membrane after its recruitment by Ras, Raf-l activation is associate d primarily with proliferation and cell survival, but it has also been implicated in apoptosis, Raf-l has also been shown to form complexes with both R-Ras and Bcl-2, raising the possibility that this component of cellular Raf-l plays a role in apoptosis, Recently, taxol was repo rted to induce Bcl-2 phosphorylation and inactivation, We have previou sly demonstrated Raf-l activation following taxol in MCF7 cells, We no w present evidence that taxol fails to stimulate either apoptosis or p hosphorylation of Bcl-2 in the absence of Raf-l, Moreover, Raf-l activ ation by taxol coincided with Bcl-2 phosphorylation, showing similar d ose and time dependence, Thus, our data support a role for a distinct subcellular component of Raf-l, which is taxol but not phorbol myrista te acetate sensitive, in mediating an apoptotic pathway involving Bcl- 2.