Apoptosis-linked gene-2 connects the Raf-1 and ASK1 signalings.
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.
Chen
Changmin
C
Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, USA. cchen3@bidmc.harvard.edu
Sytkowski
Arthur J
AJ
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; C097753:PDCD6 protein, human; D011994:Recombinant Proteins; D019908:Proto-Oncogene Proteins c-raf; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human