Abstract
The interactions between Notch (N) receptors and their transmembrane ligands, Jagged1 (JI) and Delta1 (Dl1), mediate signaling events between neighboring cells that are crucial during embryonal development and in adults. Since the non-transmembrane extracellular form of J1 acts as an antagonist of N activation in NIH 3T3 mouse fibroblast cells and induces fibroblast growth factor 1 (FGF1)-dependent transformation (Small, D., Kovalenko, D., Soldi, R., Mandinova, A., Kolev, V., Trifonova, R., Bagala, C., Kacer, D., Battelli, C., Liaw, L., Prudovsky, I., and Maciag, T. (2003) J. Biol. Chem. 278, 16405-16413), we examined the potential redundant functions of the two subfamilies of Notch ligands and report that while the soluble (s) forms of both Dl1 and J1 act as N signaling antagonists in NIH 3T3 cells, they do display disparate functions. While sJ1 induced an attenuation of cell motility which is accompanied by a decrease in actin stress fibers and an increase in adherence junctions, sDl1 does not. However, sJ1, like sDl1, induces a NIH 3T3 cell tranformed phenotype mediated by FGF signaling. Because the inhibition of N signaling by sJ1 and sDl1 is rescued by dominant-negative Src expression, we suggest that there may be cooperation between the Notch and Src signaling pathways.
Highlights
The Non-transmembrane Form of Delta1, but Not of Jagged1, Induces Normal Migratory Behavior Accompanied by Fibroblast Growth Factor Receptor 1-dependent Transformation*
We have previously demonstrated that the expression of a soluble form of Jagged1 induced significant changes in the phenotype of NIH 3T3 cells including the onset of a FGFR1dependent phenotype with impaired cell motility, associated with reduced actin stress fibers and focal adhesion sites formation [24]
To determine whether these events were soluble form of Jagged1 (sJ1)-specific, we examined the phenotype of NIH 3T3 cells stably transfected with soluble extracellular domain of Delta1
Summary
The Non-transmembrane Form of Delta1, but Not of Jagged1, Induces Normal Migratory Behavior Accompanied by Fibroblast Growth Factor Receptor 1-dependent Transformation*. We have previously demonstrated that the expression of a soluble form of Jagged1 (sJ1) induced significant changes in the phenotype of NIH 3T3 cells including the onset of a FGFR1dependent phenotype with impaired cell motility, associated with reduced actin stress fibers and focal adhesion sites formation [24].
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