A non-transmembrane form of Jagged-1 regulates the formation of matrix-dependent chord-like structures.
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.
Wong
M K
MK
Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
Prudovsky
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Vary
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Booth
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Liaw
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L
Mousa
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Small
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D
Maciag
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T
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
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