Kuo, Calvin J.LaMontagne, Kenneth R.Garcia-Cardeña, GuillermoAckley, Brian D.Kalman, DanielPark, SusanChristofferson, RolfKamihara, JunneDing, Yuan-HuaLo, Kin-MingGillies, StephenFolkman, JudahMulligan, Richard C.Javaherian, Kashi2014-10-062014-10-062001-03-19Kuo, Calvin J. 2001. "Oligomerization-dependent Regulation of Motility and Morphogenesis by the Collagen XVIII NC1/Endostatin Domain." Journal of Cell Biology, v. 1152, pp. 1233. http://www.dx.doi.org/10.1083/jcb.152.6.12330021-9525https://hdl.handle.net/1808/15178This is the publisher's version, also available electronically from http://jcb.rupress.org/content/152/6/1233.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.Collagen XVIIIendostatinMotilityMorphogenesisExtracellular matrixArticle10.1083/jcb.152.6.1233openAccess