Rubinfeld B, Tice D A, Polakis P
Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
J Biol Chem. 2001 Oct 19;276(42):39037-45. doi: 10.1074/jbc.M105148200. Epub 2001 Aug 3.
Axin and the adenomatous polyposis coli protein (APC) interact to down-regulate the proto-oncogene beta-catenin. We show that transposition of an axin-binding site can confer beta-catenin regulatory activity to a fragment of APC normally lacking this activity. The fragment containing the axin-binding site also underwent hyperphosphorylation when coexpressed with axin. The phosphorylation did not require glycogen synthase kinase 3beta but instead required casein kinase 1epsilon, which bound directly to axin. Mutation of conserved serine residues in the beta-catenin regulatory motifs of APC interfered with both axin-dependent phosphorylation and phosphorylation by CKIepsilon and impaired the ability of APC to regulate beta-catenin. These results suggest that the axin-dependent phosphorylation of APC is mediated in part by CKIepsilon and is involved in the regulation of APC function.
Axin与腺瘤性息肉病结肠蛋白（APC）相互作用，以下调原癌基因β-连环蛋白。我们发现，axin结合位点的转位可将β-连环蛋白调节活性赋予通常缺乏此活性的APC片段。当与axin共表达时，含有axin结合位点的片段也会发生超磷酸化。这种磷酸化不需要糖原合酶激酶3β，而是需要酪蛋白激酶1ε，它直接与axin结合。APC的β-连环蛋白调节基序中保守丝氨酸残基的突变会干扰axin依赖性磷酸化和CKIε介导的磷酸化，并损害APC调节β-连环蛋白的能力。这些结果表明，APC的axin依赖性磷酸化部分由CKIε介导，并参与APC功能的调节。
