由IGF-1R導致BAD磷酸化的細胞凋亡信號通路
胰島素樣生長因子-1(insulin-like growth factor,IGF-1)是胰島素樣生長因子家族中的一種,通過與IGF-1受體相結合產生生物學效應,是通過內分泌、自分泌和旁分泌的三種途徑分泌的低分子 多肽。近些年來,研究發現IGF-1不僅具有胰島素類似的功能以及介導生長激素的作用,還是多種類型細胞凋亡 的一個重要抑制因子。
IGF-1R, the type 1 receptor for insulin-like growth factor, mediates cell survival and growth in response to its ligands IGF-1 and IGF-2. This tyrosine kinase receptor is widely expressed in many cell types and is a key mediator of growth. Overexpression or activation of IGF-1R may be involved in the proliferation of transformed cells, making inhibition of IGF-1R signaling a strategy for the development of cancer drugs. IGF-1R activates three signaling pathways that converge to phosphorylate BAD protein and block apoptosis. The first pathway activated by IGF-1R stimulates PI3-kinase and the AKT pathway to phosphorylate BAD and block apoptosis. A second pathway activated by IGF-1R involves ras mediated activation of the map kinase pathway to block apoptosis. A third pathway involves interaction of raf with mitochondria in response to IGF-1R activation. The convergence of these pathways to block apoptosis may enhance the IGF-1R response.