Abstract：
:The β-catenin signaling axis is critical for normal embryonic development and tissue homeostasis in adults. We have previously shown that extracellular enzyme transglutaminase 2 (TG2) activates β-catenin signaling in vascular smooth muscle cells (VSMCs). In this study, we provide several lines of evidence that TG2 functions as an activating ligand of the LRP5/6 receptors. Specifically, we show that TG2 synergizes with LRP6 in the activation of β-catenin-dependent gene expression in Cos-7 cells. Interfering with the LRP5/6 receptors attenuates TG2-induced activation of β-catenin in Cos-7 cells. Further, we show that TG2 binds directly to the extracellular domain of LRP6, which is also able to act as a substrate for TG2-mediated protein cross-linking. Furthermore, inhibitors of TG2 protein cross-linking quench the observed TG2-induced β-catenin activation, implicating protein cross-linking as a novel regulatory mechanism for this pathway. Together, our findings identify and characterize a new activating ligand of the LRP5/6 receptors and uncover a novel activity of TG2 as an agonist of β-catenin signaling, contributing to the understanding of diverse developmental events and pathological conditions in which transglutaminase and β-catenin signaling are implicated.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Deasey S,Nurminsky D,Shanmugasundaram S,Lima F,Nurminskaya Mdoi
10.1016/j.cellsig.2013.08.016subject
Has Abstractpub_date
2013-12-01 00:00:00pages
2646-51issue
12eissn
0898-6568issn
1873-3913pii
S0898-6568(13)00251-9journal_volume
25pub_type
杂志文章abstract：:Bradykinin (BK) is released into the tear-film in ocular allergic patients. BK has been shown to exert mitogenic effects on several cell types. However, the mechanisms underlying its action on corneal keratocytes (CKs) were largely unknown. This study was to investigate the mitogenic effect of BK on rabbit CKs linked ...
journal_title：Cellular signalling
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journal_title：Cellular signalling
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2019.109439
更新日期：2020-01-01 00:00:00
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journal_title：Cellular signalling
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更新日期：2008-09-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2006.05.017
更新日期：2006-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/0898-6568(93)90075-w
更新日期：1993-07-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.03.010
更新日期：2014-07-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2011.12.009
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2004.01.006
更新日期：2004-08-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2013.04.009
更新日期：2013-10-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2016.06.010
更新日期：2016-09-01 00:00:00
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journal_title：Cellular signalling
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.03.001
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journal_title：Cellular signalling
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journal_title：Cellular signalling
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更新日期：2015-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2016.10.007
更新日期：2017-01-01 00:00:00
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pub_type： 杂志文章,评审
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(93)90071-s
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.12.014
更新日期：2015-04-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.05.008
更新日期：2013-09-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.09.019
更新日期：2014-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(99)00019-4
更新日期：1999-07-01 00:00:00
