Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth

作者: F Bussolino , M F Di Renzo , M Ziche , E Bocchietto , M Olivero

DOI: 10.1083/JCB.119.3.629

关键词: AngiogenesisHepatocyte Growth Factor ActivatorCell biologyReceptor tyrosine kinaseVascular endothelial growth factor AEndocrinologyHepatocyte growth factorEndothelial stem cellTyrosine kinaseBiologyGrowth factorInternal medicine

摘要: Hepatocyte Growth Factor (HGF, also known as Scatter Factor) is a powerful mitogen or motility factor in different cells, acting through the tyrosine kinase receptor encoded by MET protooncogene. Endothelial cells express gene and expose at cell surface mature protein (p190MET) made of 50 kD (alpha) subunit disulfide linked to 145-kD (beta) subunit. HGF binding endothelial identifies two sites with affinities. The higher affinity site (Kd = 0.35 nM) corresponds p190MET receptor. Sub-nanomolar concentrations HGF, but not recombinant inactive precursor, stimulate activity, proliferation motility. induces repairs wound monolayer. stimulates scatter grown on three-dimensional collagen gels, inducing an elongated phenotype. In rabbit cornea, highly purified promotes neovascularization sub-nanomolar concentrations. lacks activities related hemostasis-thrombosis, inflammation accessory functions. These data show that vivo potent angiogenic vitro proliferate migrate.

参考文章(75)
R P Narsimhan, L Naldini, P M Comoglio, E Vigna, G K Michalopoulos, G Gaudino, R Zarnegar, Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. Oncogene. ,vol. 6, pp. 501- 504 ,(1991)
R. P. Narsimhan, E. Medico, P. M. Comoglio, M. F. Di Renzo, S. Giordano, M. Olivero, P. Gaglia, P. Zara, S. Bretti, Expression of the Met/HGF receptor in normal and neoplastic human tissues. Oncogene. ,vol. 6, pp. 1997- 2003 ,(1991)
L. Naldini, K.M. Weidner, E. Vigna, G. Gaudino, A. Bardelli, C. Ponzetto, R.P. Narsimhan, G. Hartmann, R. Zarnegar, G.K. Michalopoulos, Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. The EMBO Journal. ,vol. 10, pp. 2867- 2878 ,(1991) , 10.1002/J.1460-2075.1991.TB07836.X
Paolo Comoglio, Silvia Giordano, Maria Flavia Di Renzo, C Rosa, Cs Cooper, Rp Narsimhan, Biosynthesis of the protein encoded by the c-met proto-oncogene. Oncogene. ,vol. 4, pp. 1383- 1388 ,(1989)
F Bussolino, F Colotta, E Bocchietto, A Bosia, E DeJana, A Sica, I M Padura, A Mantovani, M De Rossi, J M Wang, Murine endothelioma cell lines transformed by polyoma middle T oncogene as target for and producers of cytokines. Journal of Immunology. ,vol. 147, pp. 2122- 2129 ,(1991)
Robert Rothlein, Jordan S. Pober, Timothy A. Springer, Lynne A. Lapierre, Michael A. Gimbrone, Walter Fiers, Donna L. Mendrick, Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. Journal of Immunology. ,vol. 137, pp. 1893- 1896 ,(1986)
A. Graziani, D. Gramaglia, L.C. Cantley, P.M. Comoglio, The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase. Journal of Biological Chemistry. ,vol. 266, pp. 22087- 22090 ,(1991) , 10.1016/S0021-9258(18)54536-1
Alberto Mantovani, Federico Bussolino, Elisabetta Dejana, Cytokine regulation of endothelial cell function. The FASEB Journal. ,vol. 6, pp. 2591- 2599 ,(1992) , 10.1096/FASEBJ.6.8.1592209
P.M. Comoglio, M.F. Di Renzo, G. Tarone, F.G. Giancotti, L. Naldini, P.C. Marchisio, Detection of phosphotyrosine-containing proteins in the detergent-insoluble fraction of RSV-transformed fibroblasts by azobenzene phosphonate antibodies. The EMBO Journal. ,vol. 3, pp. 483- 489 ,(1984) , 10.1002/J.1460-2075.1984.TB01834.X