Oligomerization-dependent regulation of motility and morphogenesis by the collagen XVIII NC1/endostatin domain |
| |
| Authors: | Kuo C J LaMontagne K R Garcia-Cardeña G Ackley B D Kalman D Park S Christofferson R Kamihara J Ding Y H Lo K M Gillies S Folkman J Mulligan R C Javaherian K |
| |
| Affiliation: | Department of Surgery, Children's Hospital, Harvard Medical School, Boston. Massachusetts 02115, USA. cjkuo@stanford.edu |
| |
| Abstract: | Collagen XVIII (c18) is a triple helical endothelial/epithelial basement membrane protein whose noncollagenous (NC)1 region trimerizes a COOH-terminal endostatin (ES) domain conserved in vertebrates, Caenorhabditis elegans and Drosophila. Here, the c18 NC1 domain functioned as a motility-inducing factor regulating the extracellular matrix (ECM)-dependent morphogenesis of endothelial and other cell types. This motogenic activity required ES domain oligomerization, was dependent on rac, cdc42, and mitogen-activated protein kinase, and exhibited functional distinction from the archetypal motogenic scatter factors hepatocyte growth factor and macrophage stimulatory protein. The motility-inducing and mitogen-activated protein kinase-stimulating activities of c18 NC1 were blocked by its physiologic cleavage product ES monomer, consistent with a proteolysis-dependent negative feedback mechanism. These data indicate that the collagen XVIII NC1 region encodes a motogen strictly requiring ES domain oligomerization and suggest a previously unsuspected mechanism for ECM regulation of motility and morphogenesis. |
| |
| Keywords: | collagen XVIII endostatin motility morphogenesis extracellular matrix |
| 本文献已被 PubMed 等数据库收录！ |
|
