IndraLab

"The phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4EBP1) by mTOR results in the release of eukaryotic initiation factor 4E (eIF-4E) and allows its participation in the initiation of cap-dependent mRNA translation."

"Once activated, mTOR phosphorylates its downstream targets, ribosomal protein S6 kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), thereby promoting mRNA translation, protein synthesis, and cell growth xref ."

"Here we show that hydrogen peroxide (H 2 O 2 ), a major oxidant generated when oxidative stress occurs, induced apoptosis of neuronal cells (PC12 cells and primary murine neurons), by inhibiting the mammalian target of rapamycin (mTOR)-mediated phosphorylation of ribosomal p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1)."

"We also show that phosphorylation of Ser2448 does not seem to modulate in vitro phosphorylation of eukaryotic initiation factor 4E-binding protein 1 by mTOR."

"Because the mammalian target of rapamycin (mTOR)-mediated phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic translation initiation factor 4E (eIF4E), and S6 kinase ribosomal protein stimulate de novo HIF-1α protein synthesis [ xref , xref ], we further elucidated the phosphorylation status of 4E-BP1, eIF4E, and S6 kinase after vanillin treatment."

"MTOR also phosphorylates and inactivates the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) reducing its affinity for the eukaryotic initiation factor 4E (eIF4E) thus releasing eIF4E to facilitate translation initiation."

"MTOR phosphorylates p70 ribosomal S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1)."

"Activated mTOR phosphorylates ribosomal protein 6 kinase (S6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1), two factors involved in translation initiation, resulting in an increase in protein synthesis, which in turn promotes cell growth and proliferation [ xref , xref ]."

"Under non-stressed conditions, mTOR phosphorylates p70 S6 kinase (p70S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1)."

"After nighttime feeding, mTOR phosphorylates Tight Junction Protein 1 (TJP1)."

"Activated mTOR further phosphorylates ribosomal p70 S6 kinase (S6K1), eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), and Akt, controlling cell proliferation, growth, and survival. xref , xref Activated PDK1 also positively regulates S6K1. xref Studies have placed tuberous sclerosis complex (TSC) 1/2 as a modulator between PI3K/Akt and mTOR. xref - xref The TSC1/2 complex acts as a repressor of mTOR function. xref - xref TSC2 has GTPase-activating protein (GAP) activity towards the Ras family small GTPase Rheb (Ras homolog enriched in brain), and TSC1/2 antagonizes the mTOR signaling pathway via stimulation of GTP hydrolysis of Rheb. xref - xref Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38, xref though this remains controversial. xref The TSC can also be activated by energy depletion through the activation of AMP-activated kinase (AMPK). xref AMPK responds both to changes in AMP concentration and to changes in the ratio of AMP to ATP. xref An increased AMP to ATP ratio allows AMPK phosphorylation and activation. xref This, in turn, activates the TSC, which catalyzes the conversion of Rheb-GTP to Rheb-GDP and thus inhibits mTOR. xref AMPK can also be phosphorylated and activated by the calcium- and calmodulin-dependent protein kinase kinase-β (CaMKK-β) in response to alterations in intracellular calcium homeostasis. xref In addition, AMPK may be activated by oxidative stress. xref "

"The mTOR phosphorylates eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), as well as inactivates, thus reducing its combination with eIF4E and releasing eIF4E to promote the initiation of translation [ xref ]."

"One of the most important effector molecules downstream of PI3K/Akt pathway appears to be the mammalian target of rapamycin (mTOR), a key regulator of protein synthesis, which can subsequently phosphorylate S6 kinase (S6K) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1) ( xref )."

"The phosphorylation of the eIF4E binding protein 1 (4EBP1) by mTOR complex 1 (mTORC1) is a critical step by which mTOR promotes protein synthesis by enhancing cap-dependent mRNA translation xref ."

"MTOR phosphorylates the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and then phosphorylated 4E-BP1 (p4E-BP1) triggers cell cycle progression, cell proliferation and angiogenesis."

"MTOR also phosphorylates and inactivates eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), reducing its affinity for eIF4E and releasing eIF4E to facilitate translation initiation."

"The second involves the activation of mammalian target of rapamycin (mTOR) which phosphorylates the eIF4E repressor protein, 4E binding protein 1 (4EBP1) and 70 kDa ribosomal protein S6 kinase 1 (S6K1), both of which regulate the binding of mRNA to the 43S ribosomal complex."

"MTOR complex 1 (mTORC1) phosphorylates the ribosomal protein S6 kinase (S6K1) and the eIF4E binding protein 1 (4E-BP1) to positively regulate translation initiation and elongation ( xref ; xref )."

"Activated mTOR phosphorylates the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and the p70 ribosomal S6 kinase 1 (S6K1), which phosphorylates the ribosomal protein S6 and consequently regulates protein synthesis ( xref )."

"For translation initiation to occur, mTOR must increase phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), releasing eIF4E to bind to eIF4G, forming the eIF4F complex."