JAM4增强肝细胞生长因子介导的Madin-Darby犬肾细胞的分支和散射。

JAM4 enhances hepatocyte growth factor-mediated branching and scattering of Madin-Darby canine kidney cells.

作者信息

Mori Hiroki, Hirabayashi Susumu, Shirasawa Madoka, Sugimura Haruhiko, Hata Yutaka

机构信息

Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

出版信息

Genes Cells. 2004 Sep;9(9):811-9. doi: 10.1111/j.1365-2443.2004.00765.x.

DOI:10.1111/j.1365-2443.2004.00765.x

PMID:15330858

Abstract

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.

摘要

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是一种在上皮细胞紧密连接处的膜相关鸟苷酸激酶蛋白。我们制备了表达JAM4的犬肾II型（MDCK）细胞（MDCK-JAM4），并将它们与野生MDCK细胞进行比较。肝细胞生长因子（HGF）处理在MDCK-JAM4细胞中诱导出更显著的分支和散射。随后我们试图鉴定由JAM4修饰的信号通路。JAM4的过表达在COS-7细胞中诱导突起形成。尽管这些突起不同于典型的片状伪足，但Rac的显性负突变体抑制了它们。使用CDC42和PAK的Rac相互作用结合域的下拉实验也支持Rac在表达JAM4的COS-7细胞中被激活。综上所述，JAM4自身激活Rac，并可能增强HGF对Rac的激活，从而导致分支和散射的增强。