Home LiteratureArticle Details
PMID: 8692945 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 14 ·1996-07-09 ·Pages 7063-8

Wang HG, Takayama S, Rapp UR, Reed JC

Abstract

The Bcl-2 protein blocks programmed cell death (apoptosis) through an unknown mechanism. Previously we identified a Bcl-2 interacting protein BAG-1 that enhances the anti-apoptotic effects of Bcl-2. Like BAG-1, the serine/threonine protein kinase Raf-1 also can functionally cooperate with Bcl-2 in suppressing apoptosis. Here we show that Raf-1 and BAG-1 specifically interact in vitro and in yeast two-hybrid assays. Raf-1 and BAG-1 can also be coimmunoprecipitated from mammalian cells and from insect cells infected with recombinant baculoviruses encoding these proteins. Furthermore, bacterially-produced BAG-1 protein can increase the kinase activity of Raf-1 in vitro. BAG-1 also activates this mammalian kinase in yeast. These observations suggest that the Bcl-2 binding protein BAG-1 joins Ras and 14-3-3 proteins as potential activators of the kinase Raf-1.

MeSH Terms
Animals Apoptosis Carrier Proteins/metabolism Chlorocebus aethiops Cloning, Molecular DNA-Binding Proteins Enzyme Activation Glutathione Transferase Humans Kinetics Mammals Protein Serine-Threonine Kinases/metabolism Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-raf Recombinant Fusion Proteins/metabolism Saccharomyces cerevisiae/metabolism Spodoptera Transcription Factors Transfection
Chemicals
BCL2-associated athanogene 1 protein Carrier Proteins DNA-Binding Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Recombinant Fusion Proteins Transcription Factors Glutathione Transferase Protein-Tyrosine Kinases Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-raf
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Wang H G
The Burnham Institute, La Jolla, CA 92037, USA.
Takayama S
Rapp U R
Reed J C
References (30)
30 references, click to expand
  1. The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory.
    J Exp Med. 1993 Aug 1;178(2):427-38 PMID: 8340752
  2. Activation of Raf-1 by 14-3-3 proteins.
    Nature. 1994 Oct 13;371(6498):612-4 PMID: 7935795
  3. Critical tyrosine residues regulate the enzymatic and biological activity of Raf-1 kinase.
    Mol Cell Biol. 1993 Nov;13(11):7170-9 PMID: 7692235
  4. Protein kinase C-mediated serine phosphorylation directly activates Raf-1 in murine hematopoietic cells.
    J Biol Chem. 1994 Jan 14;269(2):1249-56 PMID: 8288587
  5. Bcl-2 and the regulation of programmed cell death.
    J Cell Biol. 1994 Jan;124(1-2):1-6 PMID: 8294493
  6. Interactions among members of the Bcl-2 protein family analyzed with a yeast two-hybrid system.
    Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9238-42 PMID: 7937747
  7. Interaction of the protein kinase Raf-1 with 14-3-3 proteins.
    Science. 1994 Oct 7;266(5182):126-9 PMID: 7939632
  8. Checkpoints of dueling dimers foil death wishes.
    Cell. 1994 Oct 21;79(2):189-92 PMID: 7954787
  9. Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity.
    Cell. 1995 Jan 27;80(2):279-84 PMID: 7834747
  10. The ins and outs of Raf kinases.
    Trends Biochem Sci. 1994 Nov;19(11):474-80 PMID: 7855890
  11. Apoptosis in the pathogenesis and treatment of disease.
    Science. 1995 Mar 10;267(5203):1456-62 PMID: 7878464
  12. R-Ras promotes apoptosis caused by growth factor deprivation via a Bcl-2 suppressible mechanism.
    J Cell Biol. 1995 May;129(4):1103-14 PMID: 7744959
  13. Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways.
    Nature. 1995 Jul 13;376(6536):188-91 PMID: 7603573
  14. Crystal structure of the zeta isoform of the 14-3-3 protein.
    Nature. 1995 Jul 13;376(6536):191-4 PMID: 7603574
  15. Bcl-2: prevention of apoptosis as a mechanism of drug resistance.
    Hematol Oncol Clin North Am. 1995 Apr;9(2):451-73 PMID: 7642473
  16. raf family serine/threonine protein kinases in mitogen signal transduction.
    Cold Spring Harb Symp Quant Biol. 1988;53 Pt 1:173-84 PMID: 2978288
  17. The Raf-1 kinase as a transducer of mitogenic signals.
    Cancer Cells. 1990 Dec;2(12):377-82 PMID: 2150916
  18. Differential regulation of the p72-74 RAF-1 kinase in 3T3 fibroblasts expressing ras or src oncogenes.
    Cell Growth Differ. 1991 May;2(5):235-43 PMID: 1888699
  19. The role of Raf-1 phosphorylation in signal transduction.
    Adv Cancer Res. 1992;58:53-73 PMID: 1312290
  20. Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA.
    Nature. 1993 Jan 28;361(6410):365-9 PMID: 8381212
  21. Toward an understanding of the molecular mechanisms of physiological cell death.
    Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):786-9 PMID: 8430086
  22. Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1.
    Nature. 1993 Jul 22;364(6435):308-13 PMID: 8332187
  23. Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro.
    Nature. 1993 Jul 22;364(6435):352-5 PMID: 8332195
  24. Mammalian Ras interacts directly with the serine/threonine kinase Raf.
    Cell. 1993 Jul 16;74(1):205-14 PMID: 8334704
  25. Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane.
    Nature. 1994 Jun 2;369(6479):411-4 PMID: 8196769
  26. Activation of Raf as a result of recruitment to the plasma membrane.
    Science. 1994 Jun 3;264(5164):1463-7 PMID: 7811320
  27. Apoptosis regulation by interaction of Bcl-2 protein and Raf-1 kinase.
    Oncogene. 1994 Sep;9(9):2751-6 PMID: 8058342
  28. Binding of 14-3-3 proteins to the protein kinase Raf and effects on its activation.
    Science. 1994 Sep 16;265(5179):1713-6 PMID: 8085158
  29. Stimulatory effects of yeast and mammalian 14-3-3 proteins on the Raf protein kinase.
    Science. 1994 Sep 16;265(5179):1716-9 PMID: 8085159
  30. Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes.
    Cancer Res. 1993 Oct 1;53(19):4701-14 PMID: 8402648
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.14.7063
Published
1996-07-09
Pages
7063-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38936
Subset
IM
Grants
NCI NIH HHS · CA67329 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.14.7063 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2