Gene interactions and pathways from curated databases and text-mining
Nat Cell Biol 2011, PMID: 21336308

Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1.

Zheng, Min; Wang, Yan-Hai; Wu, Xiao-Nan; Wu, Su-Qin; Lu, Bao-Ju; Dong, Meng-Qiu; Zhang, Hongbing; Sun, Peiqing; Lin, Sheng-Cai; Guan, Kun-Liang; Han, Jiahuai

Cell growth can be suppressed by stressful environments, but the role of stress pathways in this process is largely unknown. Here we show that a cascade of p38β mitogen-activated protein kinase (MAPK) and p38-regulated/activated kinase (PRAK) plays a role in energy-starvation-induced suppression of mammalian target of rapamycin (mTOR), and that energy starvation activates the p38β-PRAK cascade. Depletion of p38β or PRAK diminishes the suppression of mTOR complex 1 (mTORC1) and reduction of cell size induced by energy starvation. We show that p38β-PRAK operates independently of the known mTORC1 inactivation pathways--phosphorylation of tuberous sclerosis protein 2 (TSC2) and Raptor by AMP-activated protein kinase (AMPK)--and surprisingly, that PRAK directly regulates Ras homologue enriched in brain (Rheb), a key component of the mTORC1 pathway, by phosphorylation. Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide-binding ability of Rheb and inhibits Rheb-mediated mTORC1 activation. The direct regulation of Rheb by PRAK integrates a stress pathway with the mTORC1 pathway in response to energy depletion.

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Text Mining Data

Ras homologue enriched in brain (Rheb) → PRAK: " We show that p38ß-PRAK operates independently of the known mTORC1 inactivation pathways -- phosphorylation of tuberous sclerosis protein 2 (TSC2) and Raptor by AMP activated protein kinase (AMPK) -- and surprisingly, that PRAK directly regulates Ras homologue enriched in brain (Rheb) , a key component of the mTORC1 pathway, by phosphorylation "

mTORC1 ⊣ Rheb: " Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide binding ability of Rheb and inhibits Rheb mediated mTORC1 activation "

Rheb — PRAK: " The direct regulation of Rheb by PRAK integrates a stress pathway with the mTORC1 pathway in response to energy depletion "

Manually curated Databases

No curated data.