CD47 regulation of epithelial cell spreading and migration, and its signal transduction.
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.
Shinohara
Masahiko
M
Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan.
Ohyama
Naoko
N
Murata
Yoji
Y
Okazawa
Hideki
H
Ohnishi
Hiroshi
H
Ishikawa
Osamu
O
Matozaki
Takashi
T
D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D051928:CD47 Antigen / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004285:Dogs; D004847:Epithelial Cells / Q000502:physiology* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D051928:CD47 Antigen; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases