Abstract
mTOR complex 1 (mTORC1) is a multiprotein complex that integrates diverse signals including growth factors, nutrients, and stress to control cell growth. Raptor is an essential component of mTORC1 that functions to recruit specific substrates. Recently, Raptor was suggested to be a key target of regulation of mTORC1. Here, we show that Raptor is phosphorylated by JNK upon osmotic stress. We identified that osmotic stress induces the phosphorylation of Raptor at Ser-696, Thr-706, and Ser-863 using liquid chromatography-tandem mass spectrometry. We found that JNK is responsible for the phosphorylation. The inhibition of JNK abolishes the phosphorylation of Raptor induced by osmotic stress in cells. Furthermore, JNK physically associates with Raptor and phosphorylates Raptor in vitro, implying that JNK is responsible for the phosphorylation of Raptor. Finally, we found that osmotic stress activates mTORC1 kinase activity in a JNK-dependent manner. Our findings suggest that the molecular link between JNK and Raptor is a potential mechanism by which stress regulates the mTORC1 signaling pathway.
Highlights
MTORC1 integrates diverse signals including stress to control cell growth
Osmotic Stress Induces Raptor Phosphorylation—To explore the stresses affecting the posttranslational modification of Raptor, we examined the mobility of Raptor in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
We found that osmotic stress induced by high osmolarity sorbitol treatment retarded the mobility of Raptor (Fig. 1A)
Summary
Results: JNK phosphorylates Raptor, a component of mTORC1, and activates mTORC1 kinase upon osmotic stress. The inhibition of JNK abolishes the phosphorylation of Raptor induced by osmotic stress in cells. JNK-mediated Raptor Phosphorylation during Osmotic Stress including Raptor can function as molecular sensors for mTORC1 (12, 14 –18).
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