CD47 regulation of epithelial cell spreading and migration, and its signal transduction
CD47 regulation of epithelial cell spreading and migration, and its signal transduction
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DOI：
10.1111/j.1349-7006.2006.00245.x
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发表时间：
2006-09-01
期刊：
影响因子：
5.7
通讯作者：
Matozaki, Takashi
中科院分区：
文献类型：
--
作者：
Shinohara, Masahiko;Ohyama, Naoko;Matozaki, Takashi
CD47是一种整合素相关的五跨膜蛋白，在其细胞外区域具有免疫球蛋白样结构域。我们现在已经研究了CD47在上皮细胞扩散和迁移调控中的作用。CD47与E-cadherin共定位于上皮细胞的细胞-细胞粘附位点。Ca2+开关实验表明，CD47被内噬，然后以类似于E-cadherin的方式重新定位到细胞-细胞粘附位点。CD47的这种极化定位需要该蛋白的多跨区。CD47的强制表达诱导细胞扩散，形成明显的板状基底，导致细胞间粘附的部分破坏和肝细胞生长因子刺激的Madin-Darby犬肾细胞散射增强。cd47诱导的细胞扩散可通过抑制Src和丝裂原活化蛋白激酶激酶而被阻断。因此，这些结果表明CD47通过重组上皮细胞中的肌动蛋白细胞骨架参与了细胞间粘附和细胞迁移的调控。CD47的这一功能是由Src和丝裂原活化蛋白激酶激酶的激活介导的。
CD47 is an integrin-associated penta-transmembrane protein that possesses an immunoglobulin-like domain in its extracellular region. We have now investigated the role of CD47 in the regulation of epithelial cell spreading and migration. CD47 is colocalized with E-cadherin at cell-cell adhesion sites of epithelial cells. A Ca2+ switch experiment showed that CD47 was endocytosed and then relocalized to cell-cell adhesion sites in a similar manner to E-cadherin. Such polarized localization of CD47 required the multiple spanning region of this protein. Forced expression of CD47 induced cell spreading with marked lamellipodium formation and resulted in both partial disruption of cell-cell adhesion and enhancement of the hepatocyte growth factor-stimulated scattering of Madin-Darby canine kidney cells. The CD47-induced cell spreading was blocked by inhibition of Src and mitogen-activated protein kinase kinase. Thus, these results suggest that CD47 participates in the regulation of cell-cell adhesion and cell migration through reorganization of the actin cytoskeleton in epithelial cells. This function of CD47 is mediated by the activation of Src and mitogen-activated protein kinase kinase.