Proteomic analysis identifies that 14-3-3zeta interacts with beta-catenin and facilitates its activation by Akt.
beta-Catenin is a central effector of Wnt signaling in embryonic and stem cell development and in tumorigenesis. Here, through a mass spectrometric analysis of a beta-catenin protein complex, we identified 12 proteins as putative beta-catenin interactors. We show that one of them, 14-3-3zeta, enhances beta-catenin-dependent transcription by maintaining a high level of beta-catenin protein in the cytoplasm. More importantly, 14-3-3zeta facilitates activation of beta-catenin by the survival kinase Akt and colocalizes with activated Akt in intestinal stem cells. We propose that Akt phosphorylates beta-catenin, which results in 14-3-3zeta binding and stabilization of beta-catenin, and these interactions may be involved in stem cell development.
Tian
Qiang
Q
Institute for Systems Biology, Seattle, WA 98103, USA. qtian@systemsbiology.org
Feetham
Megan C
MC
Tao
W Andy
WA
He
Xi C
XC
Li
Linheng
L
Aebersold
Ruedi
R
Hood
Leroy
L
D048948:14-3-3 Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020543:Proteome; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
D048948:14-3-3 Proteins; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D020543:Proteome; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051176:beta Catenin; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt