Beta-catenin phosphorylated at serine 45 is spatially uncoupled from beta-catenin phosphorylated in the GSK3 domain: implications for signaling.
Beta-catenin phosphorylated at serine 45 is spatially uncoupled from beta-catenin phosphorylated in the GSK3 domain: implications for signaling.
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DOI：
10.1371/journal.pone.0010184
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发表时间：
2010-04-16
期刊：
影响因子：
3.7
通讯作者：
Gottardi CJ
中科院分区：
文献类型：
--
作者：
Maher MT;Mo R;Flozak AS;Peled ON;Gottardi CJ
线虫和果蝇在基因表达水平上产生不同的信号和黏附形式的β-连环蛋白。脊椎动物依赖于单一的β-连环蛋白基因，是否在蛋白质修饰的水平上产生独特的黏附和信号形式仍未解决。我们发现β-连环蛋白在丝氨酸37(S37)和苏氨酸41(T41)处非磷酸化，通常被称为转录活性β-连环蛋白(ABC)，在SW480细胞中是一种少量的核丰富的β-连环蛋白单体，表达低水平的E-钙粘连蛋白。尽管有早期的迹象，ABC的高信号活性并不是由于减少了钙粘素结合，因为在E-钙粘素修复的细胞中，ABC很容易被结合到钙粘附素接触中。然而，β-连环蛋白在丝氨酸45(S45)或苏氨酸41(T41)(T41/S45)或沿GSK3调节盒S33、S37或T41(S33/37/T41)被磷酸化，基本上不能与钙粘素结合。在T41/S45处磷酸化的β-catenin和在S37和T41处未磷酸化的β-catenin主要是核的，而在S33/37/T41处磷酸化的β-catenin主要是胞质的，这表明在S37和T41处的低磷酸化的DNA-catenin可能由于其促进了核积累而在转录中更活跃。T41/S45处的磷酸化与S33/37/T41处的磷酸化在空间上可以分开的证据表明，这些磷酸化可能并不总是偶联的，这增加了S45处的磷酸化发挥不同核功能的可能性。
C. elegans and Drosophila generate distinct signaling and adhesive forms of β-catenin at the level of gene expression. Whether vertebrates, which rely on a single β-catenin gene, generate unique adhesive and signaling forms at the level of protein modification remains unresolved. We show that β-catenin unphosphorylated at serine 37 (S37) and threonine 41 (T41), commonly referred to as transcriptionally Active β-Catenin (ABC), is a minor nuclear-enriched monomeric form of β-catenin in SW480 cells, which express low levels of E-cadherin. Despite earlier indications, the superior signaling activity of ABC is not due to reduced cadherin binding, as ABC is readily incorporated into cadherin contacts in E-cadherin-restored cells. β-catenin phosphorylated at serine 45 (S45) or threonine 41 (T41) (T41/S45) or along the GSK3 regulatory cassette S33, S37 or T41 (S33/37/T41), however, is largely unable to associate with cadherins. β-catenin phosphorylated at T41/S45 and unphosphorylated at S37 and T41 is predominantly nuclear, while β-catenin phosphorylated at S33/37/T41 is mostly cytoplasmic, suggesting that β-catenin hypophosphorylated at S37 and T41 may be more active in transcription due to its enhanced nuclear accumulation. Evidence that phosphorylation at T41/S45 can be spatially separated from phosphorylations at S33/37/T41 suggests that these phosphorylations may not always be coupled, raising the possibility that phosphorylation at S45 serves a distinct nuclear function.
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影响因子：
64.5
作者：
Drees, F;Pokutta, S;Weis, WI
通讯作者：
Weis, WI
DOI：
10.1083/jcb.153.5.1049
发表时间：
2001-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gottardi CJ;Wong E;Gumbiner BM
通讯作者：
Gumbiner BM
影响因子：
10.5
作者：
Brembeck, FH;Schwarz-Romond, T;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
64.8
作者：
Korswagen, HC;Herman, MA;Clevers, HC
通讯作者：
Clevers, HC
影响因子：
4.8
作者：
Giannini, AL;Vivanco, MDM;Kypta, RM
通讯作者：
Kypta, RM