Apoptosis-linked gene-2 connects the Raf-1 and ASK1 signalings

被引:24
作者
Chen, CM [1 ]
Sytkowski, AJ [1 ]
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Hematol & Oncol,Lab Cell & Mol Biol, Cambridge, MA 02138 USA
关键词
Raf-1; ALG-2; ASK1; apoptosis; signal transduction;
D O I
10.1016/j.bbrc.2005.05.074
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Raf-1 plays important roles in cell proliferation, differentiation, and survival. However, the unique and essential function of Raf-1 is anti-apoptotic. The molecules that mediate Raf-1's anti-apoptotic function are not known. In the course of identifying new substrates of Raf-1, we found that the Raf-1 kinase domain interacted with apoptosis-linked gene-2 (ALG-2) in yeast two-hybrid system. Our further studies showed that Raf-1 phosphorylated ALG-2 in an in vitro kinase assay. We also found that apoptosis signal-regulating kinase 1 (ASK1) strongly phosphorylated ALG-2. Importantly, Raf-1 blocks the ASK1-dependent ALG-2 phosphorylation. Since ALG-2 associates with ASK1, and both ASK1 and ALG-2 are involved in apoptosis, our observations indicate that Raf-1 may mediate its anti-apoptotic function by interrupting ASK1-dependent phosphorylation of ALG-2. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:51 / 57
页数:7
相关论文
共 33 条
  • [1] Role of Raf in vascular protection from distinct apoptotic stimuli
    Alavi, A
    Hood, JD
    Frausto, R
    Stupack, DG
    Cheresh, DA
    [J]. SCIENCE, 2003, 301 (5629) : 94 - 96
  • [2] Activation of apoptosis signal regulating kinase 1 (ASK1) by the adapter protein Daxx
    Chang, HY
    Nishitoh, H
    Yang, XL
    Ichijo, H
    Baltimore, D
    [J]. SCIENCE, 1998, 281 (5384) : 1860 - 1863
  • [3] Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism
    Chen, J
    Fuji, K
    Zhang, LX
    Roberts, T
    Fu, H
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (14) : 7783 - 7788
  • [4] D'Adamio L, 1997, Semin Immunol, V9, P17, DOI 10.1006/smim.1996.0057
  • [5] DENT P, 1995, MOL CELL BIOL, V15, P4125
  • [6] RAF-1 FORMS A STABLE COMPLEX WITH MEK1 AND ACTIVATES MEK1 BY SERINE PHOSPHORYLATION
    HUANG, WD
    ALESSANDRINI, A
    CREWS, CM
    ERIKSON, RL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (23) : 10947 - 10951
  • [7] MEK kinase activity is not necessary for Raf-1 function
    Hüser, M
    Luckett, J
    Chiloeches, A
    Mercer, K
    Iwobi, M
    Giblett, S
    Sun, XM
    Brown, J
    Marais, R
    Pritchard, C
    [J]. EMBO JOURNAL, 2001, 20 (08) : 1940 - 1951
  • [8] Interaction of ALG-2 with ASK1 influences ASK1 localization and subsequent JNK activation
    Hwang, IS
    Jung, YS
    Kim, E
    [J]. FEBS LETTERS, 2002, 529 (2-3) : 183 - 187
  • [9] Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways
    Ichijo, H
    Nishida, E
    Irie, K
    tenDijke, P
    Saitoh, M
    Moriguchi, T
    Takagi, M
    Matsumoto, K
    Miyazono, K
    Gotoh, Y
    [J]. SCIENCE, 1997, 275 (5296) : 90 - 94
  • [10] Structure of apoptosis-linked protein ALG-2:: Insights into Ca2+-induced changes in penta-EF-hand proteins
    Jia, J
    Tarabykina, S
    Hansen, C
    Berchtold, M
    Cygler, M
    [J]. STRUCTURE, 2001, 9 (04) : 267 - 275