title: A non-transmembrane form of Jagged-1 regulates the formation of matrix-dependent chord-like structures.
abstract: Jagged-Notch interactions regulate a transmembrane ligand-receptor signaling pathway involved in the regulation of cell fate determination as well as myoblast and endothelial cell differentiation. To further examine the role of the transmembrane ligand, Jagged-1, in the regulation of cell differentiation, we stably transfected NIH 3T3 cells with a truncated form of Jagged(J)-1, which results in the secretion of a soluble(s) form of the protein. Comparison of gene expression by serial analysis demonstrated that among the 227 transcripts differentially regulated in the sJ-1 transfectants, the expression of the pro-alpha-2(I) collagen transcript and pro-alpha-1(I) collagen translation product was predominantly repressed in sJ-1 transfectants. When plated on extracellular matrices, sJ-1 transfectants formed prominent chord-like structures on type I collagen but not on fibrin, fibronectin, or vitronectin. While the sJ-1 transfectants exhibited growth kinetics similar to control cells and were unable to grow in soft agar, the cells were less sensitive to contact inhibition of growth in vitro and sJ-1 allografts formed tissue masses in nude mice after a prolonged latency period and exhibited an abundance of host-derived microvascular endothelial cells. These data suggest that J-1 may be able to modulate, in a matrix-dependent manner, the organization of cell to cell interactions including its ability to promote the development of chord-like structures.
authors.affiliation: Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Wong
authors.forename: I
authors.initials: I
authors.lastname: Prudovsky
authors.forename: C
authors.initials: C
authors.lastname: Vary
authors.forename: C
authors.initials: C
authors.lastname: Booth
authors.forename: L
authors.initials: L
authors.lastname: Liaw
authors.forename: S
authors.initials: S
authors.lastname: Mousa
authors.forename: D
authors.initials: D
authors.lastname: Small
authors.forename: T
authors.initials: T
authors.lastname: Maciag
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D017931:DNA Primers / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D010641:Phenotype; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D000072099:Serrate-Jagged Proteins