IndraLab

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"We propose that meiotic phosphorylation of 4E-BP1 on Ser65 and Thr70 by mTOR acts to stimulate cap-dependent translation as the oocyte proceeds though meiosis (particularly after NEBD) and that specific localization of the key cap-dependent translation regulatory factors, xref is essential for the translation of specific mRNAs at the spindle area to ensure errorless meiotic progression."

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"RARRES3 overexpression induced phosphorylation of p70S6K at Thr-389 in an acyl transferase-dependent manner, downregulating mTOR by catalyzing its phosphorylation at Ser-2448 xref , xref and reducing mTOR-dependent phosphorylation of 4EBP1 at Thr-70 ( xref )."

"PHAS-I in adipocytes and HEK293 cells is phosphorylated in the following five sites, all of which conform to a (S/T)P motif (9, 10): Thr-36, Thr-45, Ser-64, Thr-69, and Ser-82. Thr-45 and Ser-64 flank the eIF4E-binding motif (7, 8), and phosphorylation of either site blocks eIF4E binding in vitro (10, 11). Insulin stimulates the phosphorylation of Thr-36, Thr-45, Ser-64, and Thr-69 in both fat cells and HEK293 cells, and incubating cells with rapamycin decreases the phosphorylation of these sites.Immunoprecipitated epitope-tagged mammalian target of rapamycin (mTOR) phosphorylated Thr-36/45. mTOR also phosphorylated Thr-69 and Ser-64 but only when purified immune complexes were incubated with the activating antibody, mTAb1."

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"Here, we show that a functional TOS motif is required for 4E-BP1 to bind to raptor (a recently identified mTOR-interacting protein), for 4E-BP1 to be efficiently phosphorylated in vitro by themTOR/raptor complex, and for 4E-BP1 to be phosphorylated in vivo at all identified mTOR-regulated sites. mTOR/raptor regulated phosphorylation is necessary for 4E-BP’s efficient release from the translational initiation factor eIF4E. We find that the TOS motif is absolutely required for efficient phosphorylation of 4E-BP1 at all the identified mTOR-regulated sites, namely, Thr37/46, Ser65, and Thr70 in vivo."

"Hyperphosphorylation of 4EBP1 by mTOR on Ser65 and Thr70 disrupts the binding of 4EBP1 to eIF4E and results in activation of cap-dependent translation [ xref , xref ]."

"mTAb1-activated mTOR phosphorylated Thr36, Thr45, Ser64, Thr69, and Ser82 in PHAS-I. All five of these sites fit a (Ser/Thr)-Pro motif and are dephosphorylated in response to rapamycin in rat adipocytes."

"MTOR-dependent phosphorylation of serine Ser 65 and N-terminal Thr 37 , Thr 46 , and Thr 70 in 4E-BP1 cleaves 4E-BP1 from the translational activator eIF-4E ( xref )."

"Mammalian target of rapamycin-dependent phosphorylation of phas-i in four (s/t)p sites detected by phospho-specific antibodies."

"Our data imply that it is unlikely that mTOR directly phosphorylates Thr69/70 in 4E-BP1."

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"4EBP1 is phosphorylated by mTOR at serine 65 and threonine 70 ( xref )."

"These results indicate that arg, leu, and gln act coordinately to stimulate proliferation of ptr cells through activation of the mtor-rps6k-rps6-eif4ebp1 signal transduction pathway. Specifically as part of mtorc1, mtor directly phosphorylates the ribosomal protein s6 kinases (s6k1 and s6k2) and the eukaryotic initiation factor 4e (eif4e)-binding proteins (4e-bp1 and 4e-bp2), both of which control specific steps in the initiation of cap-dependent translation"