A non-transmembrane form of jagged-1 regulates the formation of matrix-dependent chord-like structures

作者：Wong MKK; Prudovsky I; Vary C; Booth C; Liaw L; Mousa S; Small D; Maciag T^*

来源：Biochemical and Biophysical Research Communications, 2000, 268(3): 853-859.

DOI：10.1006/bbrc.2000.2173

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.

• 出版日期2000-2-24