Cell signaling through membrane mucins
Cell signaling through membrane mucins
复制标题
DOI：
10.1002/bies.10201
复制
发表时间：
2003-01-01
期刊：
影响因子：
4
通讯作者：
Carraway, CAC
中科院分区：
文献类型：
--
作者：
Carraway, KL;Ramsauer, VP;Carraway, CAC
MUC1和MUC4是目前研究最充分的两种膜粘蛋白。尽管它们在表面上具有相似的结构，并且都被证明对上皮表面提供立体保护，但最近的研究也表明它们与细胞信号有关。它们的作用机制完全不同，MUC4作为受体配体，MUC1作为信号分子的对接蛋白。MUC4是ErbB2/HER2/Neu受体的一种新的膜内配体，在没有其他ErbB配体的情况下触发ErbB2的特异性磷酸化，并通过在neuregin存在下形成的ErbB2/ErbB3异二聚体受体复合体增强磷酸化和信号转导。相反，MUC1具有高度保守的细胞质TALL，它结合β-连环蛋白，β-连环蛋白是黏附连接的关键成分，也是转录调节因子，这个过程受到MUC1磷酸化的严格调控。这些膜粘蛋白在上皮细胞顶端表面的特异性定位表明，它们的信号功能可能是响应上皮细胞入侵或损伤的传感机制。
MUC1 and MUC4 are the two membrane mucins that have been best characterized. Although they have superficially similar structures and have both been shown to provide steric protection of epithelial surfaces, recent studies have also implicated them in cellular signaling. They act by substantially different mechanisms, MUC4 as a receptor ligand and MUC1 as a docking protein for signaling molecules. MUC4 is a novel intramembrane ligand for the receptor tyrosine kinase ErbB2/HER2/Neu, triggering a specific phosphorylation of the ErbB2 in the absence of other ErbB ligands and potentiating phosphorylation and signaling through the ErbB2/ErbB3 heterodimeric receptor complex formed in the presence of neuregulin. In contrast, MUC1 has a highly conserved cytoplasmic tall, which binds beta-catenin, a key component of adherens junctions and a regulator of transcription, in a process that is tightly regulated by MUC1 phosphorylation. The specific localization of these membrane mucins to the apical surfaces of epithelial cells suggests that their signaling functions may be important as sensor mechanisms in response to invasion or damage of epithelia.