Phosphorylation of β-catenin by cyclic AMP-dependent protein kinase stabilizes β-catenin through inhibition of its ubiquitination

被引:342
作者
Hino, S
Tanji, C
Nakayama, KI
Kikuchi, A
机构
[1] Hiroshima Univ, Dept Biochem, Grad Sch Biomed Sci, Minami Ku, Hiroshima 7348551, Japan
[2] Kyushu Univ, Med Inst Bioregulat, Fukuoka 8128582, Japan
关键词
D O I
10.1128/MCB.25.20.9063-9072.2005
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
The mechanism of cross talk between the Wnt signaling and cyclic AMP (cAMP)-dependent protein kinase (protein kinase A [PKA]) pathways was studied. Prostaglandin E-1 (PGE(1)), isoproterenol, and dibutyryl cAMP (Bt(2)cAMP), all of which activate PKA, increased the cytoplasmic and nuclear P-catenin protein level, and these actions were suppressed by a PKA inhibitor and RNA interference for PKA. PGE(1) and Bt(2)cAMP also increased T-cell factor (Tcf)-dependent transcription through beta-catenin. Bt(2)cAMP suppressed degradation of beta-catenin at the protein level. Although PKA did not affect the formation of a complex between glycogen synthase kinase 3 beta (GSK-3 beta), beta-catenin, and Axin, phosphorylation of beta-catenin by PKA inhibited ubiquitination of beta-catenin in intact cells and in vitro. Ser675 was found to be a site for phosphorylation by PKA, and substitution of this serine residue with alanine in beta-catenin attenuated inhibition of the ubiquitination of beta-catenin by PKA, PKA-induced stabilization of beta-catenin, and PKA-dependent activation of Tcf. These results indicate that PKA inhibits the ubiquitination of beta-catenin by phosphorylating beta-catenin, thereby causing beta-catenin to accumulate and the Wnt signaling pathway to be activated.
引用
收藏
页码:9063 / 9072
页数:10
相关论文
共 43 条
[21]   Communication -: Axin, a negative regulator of the Wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of β-catenin [J].
Kishida, S ;
Yamamoto, H ;
Ikeda, S ;
Kishida, M ;
Sakamoto, I ;
Koyama, S ;
Kikuchi, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (18) :10823-10826
[22]   An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of β-catenin [J].
Kitagawa, M ;
Hatakeyama, S ;
Shirane, M ;
Matsumoto, M ;
Ishida, N ;
Hattori, K ;
Nakamichi, I ;
Kikuchi, A ;
Nakayama, K ;
Nakayama, K .
EMBO JOURNAL, 1999, 18 (09) :2401-2410
[23]   Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC(-/-) colon carcinoma [J].
Korinek, V ;
Barker, N ;
Morin, PJ ;
vanWichen, D ;
deWeger, R ;
Kinzler, KW ;
Vogelstein, B ;
Clevers, H .
SCIENCE, 1997, 275 (5307) :1784-1787
[24]   GTPASE INHIBITING MUTATIONS ACTIVATE THE ALPHA-CHAIN OF GS AND STIMULATE ADENYLYL CYCLASE IN HUMAN PITUITARY-TUMORS [J].
LANDIS, CA ;
MASTERS, SB ;
SPADA, A ;
PACE, AM ;
BOURNE, HR ;
VALLAR, L .
NATURE, 1989, 340 (6236) :692-696
[25]   Calpain as an effector of the Gq signaling pathway for inhibition of Wnt/β-catenin-regulated cell proliferation [J].
Li, G ;
Iyengar, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :13254-13259
[26]   Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism [J].
Liu, CM ;
Li, YM ;
Semenov, M ;
Han, C ;
Baeg, GH ;
Tan, Y ;
Zhang, ZH ;
Lin, XH ;
He, X .
CELL, 2002, 108 (06) :837-847
[27]   Siah-1 mediates a novel β-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein [J].
Liu, J ;
Stevens, J ;
Rote, CA ;
Yost, HJ ;
Hu, YX ;
Neufeld, KL ;
White, RL ;
Matsunami, N .
MOLECULAR CELL, 2001, 7 (05) :927-936
[28]   Negative feedback loop of Wnt signaling through upregulation of conductin/Axin2 in colorectal and liver tumors [J].
Lustig, B ;
Jerchow, B ;
Sachs, M ;
Weiler, S ;
Pietsch, T ;
Karsten, U ;
van de Wetering, M ;
Clevers, H ;
Schlag, PM ;
Birchmeier, W ;
Behrens, J .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (04) :1184-1193
[29]   2 G-PROTEIN ONCOGENES IN HUMAN ENDOCRINE TUMORS [J].
LYONS, J ;
LANDIS, CA ;
HARSH, G ;
VALLAR, L ;
GRUNEWALD, K ;
FEICHTINGER, H ;
DUH, QY ;
CLARK, OH ;
KAWASAKI, E ;
BOURNE, HR ;
MCCORMICK, F .
SCIENCE, 1990, 249 (4969) :655-659
[30]   Siah-1, SIP, and Ebi collaborate in a novel pathway for β-catenin degradation linked to p53 responses [J].
Matsuzawa, S ;
Reed, JC .
MOLECULAR CELL, 2001, 7 (05) :915-926