Bcl-2 targets the protein kinase Raf-1 to mitochondria

Hong Gang Wang, Ulf R. Rapp, John C. Reed

Research output: Contribution to journalArticlepeer-review

678 Scopus citations

Abstract

A green fluorescent protein (GFP)-Raf-1 fusion protein was used to show that Bcl-2 can target this kinase to mitochondria. Active Raf-1 fused with targeting sequences from an outer mitochondrial membrane protein protected cells from apoptosis and resulted in phosphorylation of BAD, a proapoptotic Bcl-2 homolog. Plasma membrane-targeted Raf-1 did not protect from apoptosis and resulted in phosphorylation of ERK-1 and ERK-2. Untargeted active Raf-1 improved Bcl-2-mediated resistance to apoptosis, whereas a kinase-inactive Raf-1 mutant abrogated apoptosis suppression by Bcl-2. Bcl-2 can therefore target Raf-1 to mitochondrial membranes, allowing this kinase to phosphorylate BAD or possibly other protein substrates involved in apoptosis regulation.

Original languageEnglish (US)
Pages (from-to)629-638
Number of pages10
JournalCell
Volume87
Issue number4
DOIs
StatePublished - Jan 15 1996

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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