Mechanisms of HGF induced cellular responses in endothelial cells. Panel A-HGF in the absence of ECM molecules can activate the Map kinase pathway through the Met receptor tyrosine kinase leading to a proliferative response. Panel B-HGF and co-stimulation with collagen induces activation of both the Map kinase and PI-3 kinase pathways through an unknown mechanism presumably through integrin ligation, which is Ras independent. Panel C-HGF-FN (and by analogy HGF-VN) complexes promote enhanced cellular responses by promoting the association of integrins with the Met receptor leading to the recruitment and enhanced activation of Ras, Erk 1/2 kinases and PI-3 kinase promoting both elevated proliferative and migratory responses.
Rahman et al. BMC Cell Biology 2005 6:8 doi:10.1186/1471-2121-6-8