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William Stoothoff, J. Cho, R. McDonald, G. Johnson (2005)
FRAT-2 Preferentially Increases Glycogen Synthase Kinase 3β-mediated Phosphorylation of Primed Sites, Which Results in Enhanced Tau Phosphorylation*Journal of Biological Chemistry, 280
C. Scali, F. Caraci, M. Gianfriddo, E. Diodato, R. Roncarati, G. Pollio, G. Gaviraghi, A. Copani, F. Nicoletti, G. Terstappen, A. Caricasole (2006)
Inhibition of Wnt signaling, modulation of Tau phosphorylation and induction of neuronal cell death by DKK1Neurobiology of Disease, 24
F. Cong, L. Schweizer, H. Varmus (2004)
Wnt signals across the plasma membrane to activate the β-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP, 131
P. May, Y. Reddy, J. Herz (2002)
Proteolytic Processing of Low Density Lipoprotein Receptor-related Protein Mediates Regulated Release of Its Intracellular Domain*The Journal of Biological Chemistry, 277
J. Mao, J. Mao, Ji-yong Wang, Bo Liu, Bo Liu, Weijun Pan, G. Farr, C. Flynn, Huidong Yuan, S. Takada, D. Kimelman, Lin Li, Dianqing Wu (2001)
Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway.Molecular cell, 7 4
Xi He, Mikhail Semenov, K. Tamai, Xin Zeng (2004)
LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: Arrows point the way, 131
Piyajit Watcharasit, G. Bijur, J. Zmijewski, Ling Song, Anna Zmijewska, Xinbin Chen, G. Johnson, R. Jope (2002)
Direct, activating interaction between glycogen synthase kinase-3β and p53 after DNA damageProceedings of the National Academy of Sciences of the United States of America, 99
Guizhong Liu, A. Bafico, V. Harris, S. Aaronson (2003)
A Novel Mechanism for Wnt Activation of Canonical Signaling through the LRP6 ReceptorMolecular and Cellular Biology, 23
A. Culbert, M. Brown, S. Frame, T. Hagen, D. Cross, Benjamin Bax, A. Reith (2001)
GSK‐3 inhibition by adenoviral FRAT1 overexpression is neuroprotective and induces Tau dephosphorylation and β‐catenin stabilisation without elevation of glycogen synthase activityFEBS Letters, 507
Kaihong Mi, G. Johnson (2007)
Regulated proteolytic processing of LRP6 results in release of its intracellular domainJournal of Neurochemistry, 101
S. Hino, C. Tanji, K. Nakayama, A. Kikuchi (2005)
Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase stabilizes beta-catenin through inhibition of its ubiquitination.Molecular and cellular biology, 25 20
Zhiying Zou, Brian Chung, Thao Nguyen, S. Mentone, B. Thomson, D. Biemesderfer (2004)
Linking Receptor-mediated Endocytosis and Cell SignalingJournal of Biological Chemistry, 279
S. Piao, Sunhee Lee, Hyunjoon Kim, S. Yum, J. Stamos, Yongbin Xu, Su-Jin Lee, Jaewon Lee, Sangtaek Oh, Jin-Kwan Han, Bum-Joon Park, W. Weis, N. Ha (2008)
Direct Inhibition of GSK3β by the Phosphorylated Cytoplasmic Domain of LRP6 in Wnt/β-Catenin SignalingPLoS ONE, 3
Hui-Jye Chen, Chung-Ming Lin, Chyuan-Sheng Lin, Raul Perez‐Olle, C. Leung, R. Liem (2006)
The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway.Genes & development, 20 14
Ming Hong, Danielle Chen, P. Klein, Virginia Lee (1997)
Lithium Reduces Tau Phosphorylation by Inhibition of Glycogen Synthase Kinase-3*The Journal of Biological Chemistry, 272
A. Caricasole, A. Copani, F. Caraci, E. Aronica, A. Rozemuller, A. Caruso, M. Storto, G. Gaviraghi, G. Terstappen, F. Nicoletti (2004)
Induction of Dickkopf-1, a Negative Modulator of the Wnt Pathway, Is Associated with Neuronal Degeneration in Alzheimer's BrainThe Journal of Neuroscience, 24
Hideki Yamamoto, S. Kishida, M. Kishida, S. Ikeda, S. Takada, A. Kikuchi (1999)
Phosphorylation of Axin, a Wnt Signal Negative Regulator, by Glycogen Synthase Kinase-3β Regulates Its Stability*The Journal of Biological Chemistry, 274
Xunxian Liu, J. Rubin, A. Kimmel (2005)
Rapid, Wnt-Induced Changes in GSK3β Associations that Regulate β-Catenin Stabilization Are Mediated by Gα ProteinsCurrent Biology, 15
Kaihong Mi, G. Johnson (2005)
Role of the intracellular domains of LRP5 and LRP6 in activating the Wnt canonical pathwayJournal of Cellular Biochemistry, 95
S. Yum, Su-Jin Lee, S. Piao, Yongbin Xu, J. Jung, Yunjin Jung, Sangtaek Oh, Jaewon Lee, Bum-Joon Park, N. Ha (2009)
The role of the Ser/Thr cluster in the phosphorylation of PPPSP motifs in Wnt coreceptors.Biochemical and biophysical research communications, 381 3
K. Tamai, Xin Zeng, Chunming Liu, Xinjun Zhang, Y. Harada, Z. Chang, Xi He (2004)
A mechanism for Wnt coreceptor activation.Molecular cell, 13 1
Xin Zeng, He Huang, K. Tamai, Xinjun Zhang, Y. Harada, C. Yokota, Karla Almeida, Jianbo Wang, B. Doble, J. Woodgett, A. Wynshaw-Boris, Jen-Chieh Hsieh, Xi He (2007)
Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions, 135
Jianwen Zhang, P. Krishnamurthy, G. Johnson (2002)
Cdk5 phosphorylates p53 and regulates its activityJournal of Neurochemistry, 81
H. Hoe, G. Rebeck (2005)
Regulation of ApoE receptor proteolysis by ligand binding.Brain research. Molecular brain research, 137 1-2
William Stoothoff, G. Johnson (2005)
Tau phosphorylation: physiological and pathological consequences.Biochimica et biophysica acta, 1739 2-3
R. Nusse (2005)
Cell biology: Relays at the membraneNature, 438
Xunxian Liu, J. Rubin, A. Kimmel (2005)
Rapid, Wnt-induced changes in GSK3beta associations that regulate beta-catenin stabilization are mediated by Galpha proteins.Current biology : CB, 15 22
B. MacDonald, C. Yokota, K. Tamai, Xin Zeng, Xi He (2008)
Wnt Signal Amplification via Activity, Cooperativity, and Regulation of Multiple Intracellular PPPSP Motifs in the Wnt Co-receptor LRP6*Journal of Biological Chemistry, 283
Chunming Liu, Yiming Li, Mikhail Semenov, Chun Han, G. Baeg, Yi Tan, Zhuohua Zhang, Xinhua Lin, Xi He (2002)
Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase MechanismCell, 108
Johnson (2006)
Diseases of Wnt signalingRev Endocr Metab Disord, 7
Xin Zeng, K. Tamai, B. Doble, Shitao Li, He Huang, R. Habas, H. Okamura, J. Woodgett, Xi He (2005)
A dual-kinase mechanism for Wnt co-receptor phosphorylation and activationNature, 438
N. Tolwinski, E. Wieschaus (2004)
Rethinking WNT signaling.Trends in genetics : TIG, 20 4
S. Hino, C. Tanji, K. Nakayama, A. Kikuchi (2005)
Phosphorylation of β-Catenin by Cyclic AMP-Dependent Protein Kinase Stabilizes β-Catenin through Inhibition of Its UbiquitinationMolecular and Cellular Biology, 25
GV Ferrari, RT Moon (2006)
The ups and downs of Wnt signaling in prevalent neurological disordersOncogene, 25
N. Tolwinski, E. Wieschaus (2004)
A Nuclear Function for Armadillo/β-CateninPLoS Biology, 2
G. Thomas, S. Frame, M. Goedert, I. Nathke, P. Polakis, P. Cohen (1999)
A GSK3‐binding peptide from FRAT1 selectively inhibits the GSK3‐catalysed phosphorylation of Axin and β‐cateninFEBS Letters, 458
Piyajit Watcharasit, G. Bijur, Ling Song, Jian‐hui Zhu, Xinbin Chen, R. Jope (2003)
Glycogen Synthase Kinase-3β (GSK3β) Binds to and Promotes the Actions of p53*Journal of Biological Chemistry, 278
R. Jope, G. Johnson (2004)
The glamour and gloom of glycogen synthase kinase-3.Trends in biochemical sciences, 29 2
A. Kinoshita, Tejal Shah, Michelle Tangredi, D. Strickland, B. Hyman (2003)
The Intracellular Domain of the Low Density Lipoprotein Receptor-related Protein Modulates Transactivation Mediated by Amyloid Precursor Protein and Fe65*Journal of Biological Chemistry, 278
M. Binnerts, Kyung-ah Kim, J. Bright, Sejal Patel, K. Tran, Mei Zhou, John Leung, Yi Liu, Woodrow Lomas, M. Dixon, Sophie Hazell, M. Wagle, Wen-Sheng Nie, N. Tomašević, Jason Williams, X. Zhan, Michael Levy, W. Funk, A. Abo (2007)
R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6Proceedings of the National Academy of Sciences, 104
M. Kofron, B. Birsoy, D. Houston, Qinghua Tao, C. Wylie, J. Heasman (2006)
Wnt11/β-catenin signaling in both oocytes and early embryos acts through LRP6-mediated regulation of axin, 134
Christopher Cselenyi, Kristin Jernigan, Emilios Tahinci, C. Thorne, Laura Lee, Ethan Lee (2008)
LRP6 transduces a canonical Wnt signal independently of Axin degradation by inhibiting GSK3's phosphorylation of β-cateninProceedings of the National Academy of Sciences, 105
Mark Johnson, N. Rajamannan (2007)
Diseases of Wnt signalingReviews in Endocrine and Metabolic Disorders, 8
Piyajit Watcharasit, G. Bijur, Ling Song, Jianhui Zhu, Xinbin Chen, R. Jope (2003)
Glycogen synthase kinase-3beta (GSK3beta) binds to and promotes the actions of p53.The Journal of biological chemistry, 278 49
(2007)
Wnt11/ beta-catenin signaling in both oocytes and early embryos acts through LRP6mediated regulation of axin
M. Gordon, R. Nusse (2006)
Wnt Signaling: Multiple Pathways, Multiple Receptors, and Multiple Transcription Factors*Journal of Biological Chemistry, 281
J. Bilić, Ya-Lin Huang, G. Davidson, T. Zimmermann, Cristina Cruciat, M. Bienz, C. Niehrs (2007)
Wnt Induces LRP6 Signalosomes and Promotes Dishevelled-Dependent LRP6 PhosphorylationScience, 316
(2004)
A nuclear function for armadillo/betacatenin
Chunming Liu, Yiming Li, Mikhail Semenov, Chun Han, G. Baeg, Yi Tan, Zhuohua Zhang, Xinhua Lin, Xi He (2002)
Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism.Cell, 108 6
Joshua Wolf, Todd Palmby, J. Gavard, B. Williams, J. Gutkind (2008)
Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6FEBS Letters, 582
K. Willert, S. Shibamoto, R. Nusse (1999)
Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex.Genes & development, 13 14
(2008)
Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling
M. Hart, R. Santos, I. Albert, B. Rubinfeld, P. Polakis (1998)
Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta.Current biology : CB, 8 10
Kaihong Mi, P. Dolan, G. Johnson (2006)
The Low Density Lipoprotein Receptor-related Protein 6 Interacts with Glycogen Synthase Kinase 3 and Attenuates Activity*Journal of Biological Chemistry, 281
M. Hart, R. Santos, I. Albert, B. Rubinfeld, P. Polakis (1998)
Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3βCurrent Biology, 8
N. Tolwinski, M. Wehrli, A. Rives, Naz Erdeniz, S. DiNardo, E. Wieschaus (2003)
Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity.Developmental cell, 4 3
The canonical Wnt/β‐catenin signaling pathway plays a critical role in numerous physiological and pathological processes. LRP6 is an essential co‐receptor for Wnt/β‐catenin signaling; as transduction of the Wnt signal is strongly dependent upon GSK3β‐mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane‐anchored LRP6 intracellular domain. Previously, we showed that the free LRP6 intracellular domain (LRP6‐ICD) can activate the Wnt/β‐catenin pathway in a β‐catenin and TCF/LEF‐1 dependent manner, as well as interact with and attenuate GSK3β activity. However, it is unknown if the ability of LRP6‐ICD to attenuate GSK3β activity and modulate activation of the Wnt/β‐catenin pathway requires phosphorylation of the LRP6‐ICD PPP(S/T)P motifs, in a manner similar to the membrane‐anchored LRP6 intracellular domain. Here we provide evidence that the LRP6‐ICD does not have to be phosphorylated at its PPP(S/T)P motif by GSK3β to stabilize endogenous cytosolic β‐catenin resulting in activation of TCF/LEF‐1 and the Wnt/β‐catenin pathway. LRP6‐ICD and a mutant in which all 5 PPP(S/T)P motifs were changed to PPP(A)P motifs equivalently interacted with and attenuated GSK3β activity in vitro, and both constructs inhibited the in situ GSK3β‐mediated phosphorylation of β‐catenin and tau to the same extent. These data indicate that the LRP6‐ICD attenuates GSK3β activity similar to other GSK3β binding proteins, and is not a result of it being a GSK3β substrate. Our findings suggest the functional and regulatory mechanisms governing the free LRP6‐ICD may be distinct from membrane‐anchored LRP6, and that release of the LRP6‐ICD may provide a complimentary signaling cascade capable of modulating Wnt‐dependent gene expression. J. Cell. Biochem. 108: 886–895, 2009. © 2009 Wiley‐Liss, Inc.
Journal of Cellular Biochemistry – Wiley
Published: Jan 1, 2009
Keywords: ; ; ;
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