IndraLab

"A recent study [ xref ] indicated that MCPyV -ST expression was required for the Merkel cell tumor growth in vitro and was observed to act downstream in the mammalian target of rapamycin (mTOR) signaling pathway to preserve eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) hyperphosphorylation, resulting in dysregulated cap-dependent translation and that 4E-BP1 inhibition is required for MCPyV transformation."

"Casein kinase Iepsilon (CKIepsilon), a central component of the circadian clock, interacts with and phosphorylates human period protein 1 (hPER1) [Keesler, G.A. et al. (2000) NeuroReport 5, 951-955]."

"AA did not activate Akt phosphorylation at Ser(473), but significantly increased the phosphorylation of both eukaryotic initiation factor 4E-binding protein 1 (P < 0.04) and p70(S6K) (P < 0.001)."

"C-terminal binding protein 1 phosphorylation and inactivation by Pak1 may induce putative genes by derepression [ xref ]."

"Activation of mTOR by different environmental and nutritional stimuli triggers transduction of proliferative signals by the phosphorylation of two key downstream effectors, the p70 S6 kinase and the eukaryotic initiation factor 4E binding protein 1 (4EBP-1; xref )."

"Up-regulation of mTOR results in dysregulation of cell cycle controls by phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4EBP1) and ribosomal S6 kinase (S6K), both of which increase translation of cell proliferation and survival proteins ( xref )."

"One key step of this pathway is the phosphorylation of cyclic AMP response element binding protein 1 (CREB1), a transcription factor that directly regulates the expression of several genes involved in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Since phosphorylation of S6 at Ser235/236 sites is regulated by both mTORC1 and mitogen-activated protein kinases xref we confirmed mTORC1 involvement by western blot analyses and showed decreased expression of pRAPTOR (Ser792) and increased phosphorylation of S6 (Ser235/236; pS6/S6 ratio: 12.3±1.9 mutant/8.2±1.9 control) and eukaryotic translation initiation factor 4E-Binding Protein 1 (4EBP1, Thr37/46; p4EBP1/4EBP1 ratio: 0.8±0.0 mutant/0.5±0.1 control) in the mutant oviducts (n = 3) ( xref )."

"Cap-dependent translation is facilitated by mTOR's phosphorylation and inactivation of eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), the suppressor of eIF4E (Lin et al., 1994) ."

"Recently, we have shown that curcumin inhibits phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), two downstream effector molecules of the mammalian target of rapamycin complex 1 (mTORC1) in numerous cancer cell lines."

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"Upon the TCR/CD28 activation, PKC-θ phosphorylates membrane-associated guanylate kinase (MAGUK) domain-containing protein 1 (CARMA1) on its serine residues, resulting in the recruitment of B-cell lymphoma/leukemia 10 (BCL10) and mucosa-associated lymphoid tissue 1 (MALT1) to form an active CARMA1–BCL10–MALT1 signaling complex."

"MTORC1 phosphorylates S6 kinase, S6 ribosomal protein and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) which together increase protein translation and cell proliferation [ xref , xref - xref ]."

"MTORC1 phosphorylates p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), and regulates cell growth, proliferation, survival and motility."

"While mTORC1 phosphorylates p70S6kinase (S6K) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1) to increase protein synthesis, mTORC2 directly phosphorylates Akt, enhancing its kinase acti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"As we previously found, expression of wild-type UCH-L1 inhibits the mTORC1 phosphorylation of p70 S6 kinase (S6K) and the eIF4E binding protein 1 (4EBP1) and increases the phosphorylation of AKT S473 (Fig. xref a, b)."

"Furthermore, mTORC1 positively regulates phosphorylation of S6K (at the Threonine 389 residue) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), which together control protein translation ( xref )."

"MTORC1 phosphorylates two downstream targets, p70 S6K1 and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), regulating protein translation, cell size, cell proliferation, and survival."

"Upon activation, mTORC1 directly phosphorylates the eukaryotic translation initiation factor 4E (eIF4E) binding protein 1 (4E-BP1) and S6 kinase 1 (S6K1) to promote protein synthesis [ xref ]."

"When active, mTORC1 phosphorylates the translational regulators eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1) and S6 kinase 1 (S6K1)."

"In addition, mTORC1 directly phosphorylates the eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1)."

"In addition, activated mTORC1 phosphorylates the eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) at Thr37/46, which prevents 4EBP1 from associating and thus repressing the eukary[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"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)."

"PAK1 also phosphorylates C-terminal binding protein 1 of the E1A/brefeldin A ADP ribosylated substrate (CtBP/BARS), a component of the membrane fission machinery, and this phosphorylation is critical for fission of the macropinocytic cup xref xref ."

"Pak1 phosphorylates C-terminal binding protein 1 of the E1A/brefeldin A ADP ribosylated substrate (CtBP/BARS) and modulates the contractile activity of myosin II at the macropinocytic cup."

"The process follows the epidermal growth-factor (EGF)-dependent macropinocytic pathway with macropinosome closure depending on PAK1-dependent phosphorylation of the C-terminal binding protein 1 (CtBP1/BARS) [ xref ]."

"C-terminal binding protein 1 phosphorylation and inactivation by Pak1 may induce putative genes by derepression [ xref ]."

"Upon DNA damage RNF8 detects motifs in mediator of DNA damage checkpoint protein 1 (MDC1) previously phosphorylated by ATM and performs K63-linked monoubiquitylation of histones H2A and H2AX."

"One of the key initiating steps in the damage response is the phosphorylation of human ssDNA binding protein 1 (hSSB1) by ATM."

"One of DDR proteins is mediator of DNA-damage checkpoint protein 1 (MDC1), which is phosphorylated by ATM and binds γH2AX."

"In contrast to SV40 sT and MCV LT, MCV sT exhibits oncogenic activity: it transforms rodent fibroblasts and promotes serum-independent growth of human fibroblasts. xref This is because MCV sT functions differently from SV40 sT; MCV sT promotes eukaryotic translation initiation factor 4E-binding protein 1 hyperphosphorylation and cap-dependent translation in a PP2A-independent manner, xref whereas SV40 sT induces dephosphorylation of 4E-binding protein 1 in a PP2A-dependent manner and inhibits cap-dependent translation. xref Moreover, MCV sT suppresses the activity of the E3 ubiqitin ligase SCF Fbw7 , which degrades MCV LT, and stabilizes MCV LT through its LT-stabilization domain; xref SV40 sT does not have an LT-stabilization domain."

"In contrast to SV40 sT and MCV LT, MCV sT exhibits oncogenic activity: it transforms rodent fibroblasts and promotes serum-independent growth of human fibroblasts. xref This is because MCV sT functions differently from SV40 sT; MCV sT promotes eukaryotic translation initiation factor 4E-binding protein 1 hyperphosphorylation and cap-dependent translation in a PP2A-independent manner, xref whereas SV40 sT induces dephosphorylation of 4E-binding protein 1 in a PP2A-dependent manner and inhibits cap-dependent translation. xref Moreover, MCV sT suppresses the activity of the E3 ubiqitin ligase SCF Fbw7 , which degrades MCV LT, and stabilizes MCV LT through its LT-stabilization domain; xref SV40 sT does not have an LT-stabilization domain."

"These translation regulators are p70 S6 kinase, which phosphorylates ribosomal protein S6, and eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1), which both lie downstream of the mammalian target of rapamycin (mTOR)."

"This activity can only partially be explained by the known regulatory negative feedback loop of the Akt-mTORC1 signaling pathway mediated by S6K1 phosphorylation of the Insulin Receptor Substrate Protein 1 (IRS1) ( xref )."

"Refeeding was also associated with an increase in ribosomal protein S6 phosphorylation and phosphorylation of the eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1)."

"Using immunofluorescence, we next determined expression of phosphorylated ribosomal protein S6 (phospho-S6) and phosphorylated eukaryotic initiation factor 4E-binding protein 1 (phospho-4E-BP1), well established downstream effectors of the mTOR kinase within mTORC1 ( xref )."

"In the nucleus, PKA phosphorylates cyclic AMP response element binding protein 1 (CREB-1)."

"PKA in turn phosphorylates the pro-fission dynamin related protein 1 (DRP1) that is therefore retained in the cytoplasm, leading to unopposed mitochondrial fusion."

"AAPK phosphorylates AAPK-interacting protein 1, which is an RNA-binding protein A/B ( xref )."

"mTOR is a serine-threonine protein kinase that phosphorylates ribosomal protein S6 kinase and eIF-4E binding protein 1, which increases the rate of translation of HIF-1α mRNA into protein [ xref ]."

"Mitochondrial ERK2 translocation emulates 6‐OHDA‐mediated effects on mitophagy. xref Additionally, mitochondrially localized ERK1/2 can phosphorylate dynamin‐related protein 1 (Drp‐1) and Mfn1 to impair fusion."

"We previously reported that ERK 1/2 phosphorylates the mitochondrial fission protein dynamin related protein 1 (Drp1) and induces the activation of mitochondrial fission and ROS production [ 36 ]."

"Regarding the inhibitory role of Cdk5 at synapses, Cdk5-dependent phosphorylation of the Rho guanine nucleotide exchange factor ephexin1 or the Wiskott–Aldrich syndrome protein family verprolin homologous protein 1 (WAVE1) reduces the number of dendritic spines through the modulation of actin dynamics xref xref ."

"CDK5 phosphorylates Wiskott-Aldrich syndrome protein-family verprolin homologous protein 1 (WAVE-1) to inhibit actin polymerisation [ xref ]."

"This negative effect could be explained by the phosphorylation and stabilization of HMG-box protein 1 (HBP1) by p38 MAPK."

"Upon binding of HGF to MET, the kinase domain phosphorylates growth factor receptor-bound protein 2 (GRB2) and GRB2-associated binding protein 1 (GAB1) and activates diverse downstream signaling pathways important in cancer, including the ERK/MAPK, PI3K-Akt/PKB, Crk-Rap, and Rac-Pak pathways [ xref ]."

"We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90."

"Mammalian TOR phosphorylates the translation initiation factor 4E binding protein 1 (4E-BP1), which reduces its affinity for the eukaryotic initiation factor 4E (eIF4E), thus allowing eIF4E to function in mRNA translation."

"AKT also acts on the mammalian target of rapamycin (mTOR), a multi-domain Serine/Threonine kinase that phosphorylates eukaryotic initiation factor 4E binding protein 1 (4EBP1), which inactivates eIF4E, allowing initiation of translation."

"Here we show that the Rho-dependent protein kinase ROCK phosphorylates the C-terminal residues Ser1131, Ser1137, and Thr1141 of formin homology domain protein 1 (FHOD1), a major endothelial formin that is normally autoinhibited by intramolecular interaction between the N- and C-terminal regions."

"Furthermore, Rheb induces phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and causes 4E-BP1 to dissociate from eIF4E. This dissociation is completely sensitive to rapamycin (an mTOR inhibitor) but not wortmannin (a phosphoinositide 3-kinase [PI3K] inhibitor)."

"An activated Pyk2 causes the phosphorylation of a multiple-domain Arf-GAP protein 1 (AMAP1) (other names: DDEF1 and ASAP1) [ xref ]."

"Once activated, Psk1 may phosphorylate poly(A)-binding protein binding protein 1 (Pab1 binding protein, or Pbp1), which is known to stimulate stress granule formation and inhibit TORC1 through sequestration ( xref )."

"These findings show that tPA induces Tyr(4507) phosphorylation of LDL receptor-related protein 1, which in turn leads to the downstream phosphorylation of Erk1/2, p90RSK, and GSK3β, followed by the induction of cyclin D1 in murine interstitial fibroblasts."

"It was also reported that PINK1 phosphorylates tumor necrosis factor receptor-associated protein 1 (TRAP1), and in turn TRAP1 prevents oxidative stress by preventing mitochondria from releasing cytochrome c ­­­ a crucial step in cell death."

"Further insight into the molecular mechanisms shows the suppression of phosphorylation in eukaryotic initiation factor 4E-binding protein 1 (4EBP1) by nicotinamide, whereas, an increased expression of bcl-2 and p38 and phosphorylation of 4EBP1 by TSA."

"Insulin receptor substrate protein 1 is phosphorylated by the insulin receptor and is then able to bind GRB2, which then activates the mitogen-activated protein kinase pathway through its interaction with SOS."

"TSC1 and TSC2 products, Harmatin and Tuberin, form the functional complex to serve as the negative regulator for insulin-induced phosphorylation of S6 kinase and elF4E-binding protein 1."

"In addition, PERK phosphorylates Kelch-like Ech-related protein 1, which releases Nrf2 from inhibition and translocates into the nucleus to activate the expression of antioxidant and detoxifying enzymes ( xref )."

"Activated AMPK by GTPase dynamin related protein 1 (DRP1) phosphorylation prevents ER and mitochondrial alteration in stressed β cells [ xref ]."

"With mTOR, WISP1 can activate this pathway and phosphorylate the mTOR down-stream components of p70 ribosomal S6 kinase (p70S6K) and the eukaryotic initiation factor 4E-binding protein 1 (4EBP1) ( xref , xref )."