Intracellular Signaling Molecules in Angiogenesis
Angiogenesis is regulated by multiple ligand-receptor interactions, which activate intracellular signaling pathways that promote endothelial cell activation. For example, VEGFs and FGFs bind to tyrosine kinase receptors that dimerize upon ligand-binding and undergo autophosphorylation. Phosphorylation of these receptors leads to the recruitment of adaptor molecules and the activation of several intracellular kinases including mitogen-activated protein kinases (MAPKs), PLC-gamma, PKC, PI 3-K, and Akt/PKB. Activation of these kinases leads to a cascade of phosphorylation reactions with multiple outcomes. One outcome is the transcriptional activation of target genes that promote endothelial cell survival and proliferation. Another outcome is the activation of factors that can promote cytoskeletal reorganization and cell motility. Intracellular signaling pathways direct endothelial cell activities and ultimately promote or inhibit angiogenesis.