Peruzzi F, Prisco M, Dews M, Salomoni P, Grassilli E, Romano G, Calabretta B, Baserga R
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Mol Cell Biol. 1999 Oct;19(10):7203-15. doi: 10.1128/MCB.19.10.7203.
The type 1 insulin-like growth factor receptor (IGF-1R), activated by its ligands, protects several cell types from a variety of apoptotic injuries. The main signaling pathway for IGF-1R-mediated protection from apoptosis has been previously elucidated and rests on the activation of phosphatidylinositol 3-kinase, Akt/protein kinase B, and the phosphorylation and inactivation of BAD, a member of the Bcl-2 family of proteins. In 32D cells (a murine hemopoietic cell line devoid of insulin receptor substrate 1 [IRS-1]), the IGF-1R activates alternative pathways for protection from apoptosis induced by withdrawal of interleukin-3. One of these pathways leads to the activation of mitogen-activated protein kinase, while a third pathway results in the mitochondrial translocation of Raf and depends on the integrity of a group of serines in the C terminus of the receptor that are known to interact with 14.3.3 proteins. All three pathways, however, result in BAD phosphorylation. The presence of multiple antiapoptotic pathways may explain the remarkable efficacy of the IGF-1R in protecting cells from apoptosis.
1型胰岛素样生长因子受体（IGF-1R）在其配体激活后，可保护多种细胞类型免受多种凋亡性损伤。此前已阐明IGF-1R介导的抗凋亡保护作用的主要信号通路，该通路依赖于磷脂酰肌醇3激酶、Akt/蛋白激酶B的激活以及Bcl-2蛋白家族成员BAD的磷酸化和失活。在32D细胞（一种缺乏胰岛素受体底物1 [IRS-1]的小鼠造血细胞系）中，IGF-1R激活替代通路以保护细胞免受因白细胞介素-3撤除诱导的凋亡。其中一条通路导致丝裂原活化蛋白激酶的激活，而第三条通路导致Raf向线粒体转位，且依赖于受体C末端一组已知与14.3.3蛋白相互作用的丝氨酸的完整性。然而，所有这三条通路均导致BAD磷酸化。多种抗凋亡通路的存在可能解释了IGF-1R在保护细胞免受凋亡方面的显著功效。
