The modulation of IGF-1 signalling by the intestine-specific factor CDX2.
The modulation of IGF-1 signalling by the intestine-specific factor CDX2.
复制标题
肠道特异性因子 CDX2 对 IGF-1 信号传导的调节。
DOI：
10.1136/gut.2009.179291
复制
发表时间：
2009
期刊：
影响因子：
24.5
通讯作者：
Lynch,JohnP
中科院分区：
文献类型：
--
作者：
Liu,JesseK;Lynch,JohnP
Cell surface receptors, when bound by their ligands, initiate intracellular signalling cascades that ultimately serve to modulate cell proliferation and growth, metabolism, survival and differentiation. Critical to the initiation and progression of these cascades are adaptor proteins such as the insulin receptor substrate (IRS) proteins. IRS proteins are a small family (IRS1–IRS6) of structurally related intracellular signalling adaptors that serve as scaffolding proteins, linking the activated receptor to their downstream effectors such as the phospatidylinositol-3!-kinase (PI3K) and Ras/Erk pathways. 1 Originally identified as components of insulin receptor signalling, IRS factors are now known to serve as critical intermediates for the insulin-like growth factor I receptor (IGF-1R), as well as other receptor tyrosine kinases. The IRS family of adaptors has captured the attention of clinicians and scientists alike since they have been implicated in a number of human cancers. 1 Given this critical role in both normal cell physiology and human pathologies, understanding how tissue-specific factors regulate their expression and thereby modulate IGF-1R signalling is of great importance. In this issue of Gut (see page 1250), Antonio Moschetta and colleagues present new findings on the intestinal localisation of IRS2 and the effects of CDX2 (caudalrelated homeobox protein 2) on IRS2 expression. 2 Through a careful series of experiments, they shed new light on the direct control of IRS2 and possibly IGF-1R signalling by the tissue-specific transcription factor CDX2.CDX2 is a homeodomain protein related to the Drosophila Caudal gene. It is necessary for the development and differentiation of the intestinal epithelium, 3 in which it regulates a variety of processes including intestine-specific gene expression, cell–cell adhesion, columnar morphogenesis, apoptosis and proliferation. 4 CDX2 expression has been proposed to regulate Wnt/b-catenin signalling, and enhance epidermal growth factor receptor
