mTORC1 directly inhibits AMPK to promote cell proliferation under nutrient stress.

Central to cellular metabolism and cell proliferation are highly conserved signalling pathways controlled by mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), dysregulation of which are implicated in pathogenesis of major human diseases such as cancer and type 2 diabetes. AMPK pathways leading to reduced cell proliferation are well established and, in part, act through inhibition of TOR complex-1 (TORC1) activity. Here we demonstrate reciprocal regulation, specifically that TORC1 directly down-regulates AMPK signalling by phosphorylating the evolutionarily conserved residue Ser367 in the fission yeast AMPK catalytic subunit Ssp2, and AMPK α1Ser347/α2Ser345 in the mammalian homologs, which is associated with reduced phosphorylation of activation loop Thr172.

Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling.

AMP-activated kinase (AMPK) and target of rapamycin (TOR) signalling coordinate cell growth, proliferation, metabolism and cell survival with the nutrient environment of cells. The poor vasculature and nutritional stress experienced by cells in solid tumours raises the question: how do they assimilate sufficient nutrients to survive? Here, we show that human and fission yeast cells import ATP and AMP from their external environment to regulate AMPK and TOR signalling. Exposure of fission yeast () and human cells to external AMP impeded cell growth; however, in yeast this restraining impact required AMPK.

Palladium-Mediated Synthesis of a Near-Infrared Fluorescent K Sensor.

Potassium (K) exits electrically excitable cells during normal and pathophysiological activity. Currently, K-sensitive electrodes and electrical measurements are the primary tools to detect K fluxes. Here, we describe the synthesis of a near-IR, oxazine fluorescent K sensor (K-1) with a dissociation constant suited for detecting changes in intracellular and extracellular K concentrations.

Nitrogen regulates AMPK to control TORC1 signaling.

Background: Cell growth and cell-cycle progression are tightly coordinated to enable cells to adjust their size (timing of division) to the demands of proliferation in varying nutritional environments. In fission yeast, nitrogen stress results in sustained proliferation at a reduced size.

Results: Here, we show that cells can sense nitrogen stress to reduce target of rapamycin complex-1 (TORC1) activity.