JAM4 enhances hepatocyte growth factor-mediated branching and scattering of Madin-Darby canine kidney cells
JAM4 enhances hepatocyte growth factor-mediated branching and scattering of Madin-Darby canine kidney cells
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DOI：
10.1111/j.1365-2443.2004.00765.x
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发表时间：
2004-09-01
期刊：
影响因子：
2.1
通讯作者：
Hata, Y
中科院分区：
文献类型：
--
作者：
Mori, H;Hirabayashi, S;Hata, Y
连接黏附分子(JAM)4是免疫球蛋白超家族的成员，它与MAGI-1相互作用，MAGI-1是一种膜相关的鸟苷酸激酶蛋白，位于上皮细胞的紧密连接处。我们制备了表达JAM4的狗肾细胞MDCK(MDCK-JAM4)，并与野生型MDCK细胞进行了比较。肝细胞生长因子(HGF)处理后，MDCK-JAM4细胞的分枝和散在现象更加明显。随后，我们试图确定JAM4修饰的信号通路。JAM4过表达可诱导COS-7细胞形成突起。虽然这些突起与典型的片状脂体不同，但Rac的显性负性突变体抑制了它们。使用CDC42和PAK的RAC相互结合域的下拉分析也支持在表达JAM4的COS-7细胞中激活RAC。综上所述，JAM4本身激活RAC，并可能通过HGF增强RAC的激活，导致分支和散布的增强。
Junctional adhesion molecule (JAM) 4 is a member of immunoglobulin superfamily that interacts with MAGI-1, a membrane-associated guanylate kinase protein at tight junctions in epithelial cells. We prepared Madin-Darby canine kidney II (MDCK) cells expressing JAM4 (MDCK-JAM4) and compared them with wild MDCK cells. The treatment of hepatocyte growth factor (HGF) induced more prominent branching and scattering in MDCK-JAM4 cells. Subsequently we attempted to identify signalling pathways modified by JAM4. The over-expression of JAM4 induced the formation of protrusions in COS-7 cells. Although those protrusions were different from typical lamellipodia, the dominant negative mutant of Rac suppressed them. The pull-down assay using CDC42 and Rac interactive binding domain of PAK also supports that Rac is activated in COS-7 cells expressing JAM4. Taken together, JAM4 itself activates Rac and may augment Rac activation by HGF, resulting in the enhancement of branching and scattering.