mTORC2招募并选择性磷酸化Akt的结构基础

Full article and list of author affiliations: https://doi.org/10.1126/ science.adv7111 Martin S. Taylor†, Maggie Chen†, Matthew Hancock†, Maximilian Wranik†, et al. INTRODUCTION: The protein kinase mechanistic target of rapamycin (mTOR) plays a central role in the control of cell growth, metabolism, and proliferation. Aberrant mTOR signaling contributes to aging, diabetes, and many cancers. By recruiting specific adapter proteins, mTOR forms two mutually exclusive megadalton-scale complexes—mTORC1 and mTORC2—that localize to different cellular membranes and phosphorylate specific substrates as parts of distinct but interconnected signaling networks. Inhibiting mTOR, which suppresses both complexes, is toxic. Selective blockage of individual complexes holds therapeutic promise, yet such strategies remain elusive. mTORC1, which localizes to lysosomes, responds to nutrient and stress signals. …