JAM4 enhances hepatocyte growth factor-mediated branching and scattering of Madin-Darby canine kidney cells.
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.
Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Hiroki
H
Mori
Susumu
S
Hirabayashi
Madoka
M
Shirasawa
Haruhiko
H
Sugimura
Yutaka
Y
Hata
D000818:Animals; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D002522:Chlorocebus aethiops; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007668:Kidney / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009154:Mutation; D011554:Pseudopodia / Q000648:ultrastructure; D051381:Rats; D014513:Ureter / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics
D015815:Cell Adhesion Molecules; C492399:Igsf5 protein, rat; D017228:Hepatocyte Growth Factor; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein