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.
Mori
Hiroki
H
Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Hirabayashi
Susumu
S
Shirasawa
Madoka
M
Sugimura
Haruhiko
H
Hata
Yutaka
Y
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