Signaling angiogenesis via p42/p44 MAP kinase and hypoxia

摘要: Angiogenesis is associated with a number of pathological situations. In this study, we have focused our attention on the role p42/p44 MAP (mitogen-activated protein) kinases and hypoxia in control angiogenesis. We demonstrate that play pivotal angiogenesis by exerting determinant action at three levels: i) persistent activation abrogates apoptosis; ii) kinase activity critical for controlling proliferation growth arrest confluent endothelial cells; iii) promote VEGF (vascular factor) expression activating its transcription via recruitment AP-2/Sp1 (activator protein-2) complex proximal region (-88/-66) promoter direct phosphorylation hypoxia-inducible factor 1 alpha (HIF-1 alpha). HIF-1 plays crucial activity, which mediates hypoxia-induced expression. show oxygen-regulated protein levels are not affected intracellular localization (nucleus versus cytoplasm). Finally, propose model suggests an autoregulatory feedback mechanism therefore HIF-1-dependent gene