共 43 条
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
论文数: 0 引用数: 0
h-index: 0
机构: Hiroshima Univ, Dept Biochem, Grad Sch Biomed Sci, Minami Ku, Hiroshima 7348551, Japan

Tanji, C
论文数: 0 引用数: 0
h-index: 0
机构: Hiroshima Univ, Dept Biochem, Grad Sch Biomed Sci, Minami Ku, Hiroshima 7348551, Japan

Nakayama, KI
论文数: 0 引用数: 0
h-index: 0
机构: Hiroshima Univ, Dept Biochem, Grad Sch Biomed Sci, Minami Ku, Hiroshima 7348551, Japan

Kikuchi, A
论文数: 0 引用数: 0
h-index: 0
机构: Hiroshima Univ, Dept Biochem, Grad Sch Biomed Sci, Minami Ku, Hiroshima 7348551, Japan
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.
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页码:9063 / 9072
页数:10
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