Regulation of eIF-4E BP1 Phosphorylation by mTOR

The proteins eIF-4E BP1 and p70 S6 kinase each undergo an insulin/mitogen-stimulated phosphorylation in situ that is partially inhibited by rapamycin. Previous work has established that the protein known as mTOR/RAFT-1/FRAP is the target through which the rapamycin·FKBP12 complex acts to dephosphorylate/deactivate the p70 S6 kinase; thus, some mTOR mutants that have lost the ability to bind to the rapamycin·FKBP12 complex in vitro can protect the p70 S6 kinase against rapamycin-induced dephosphorylation/deactivationin situ. We show herein that such mTOR mutants also protect eIF-4E BP1 against rapamycin-induced dephosphorylation, and for both p70 S6 kinase and eIF-4E BP1, such protection that the mTOR an mutants p70 S6 kinase to by in situ to protect eIF-4E BP1 rapamycin-induced We that mTOR is an eIF-4E BP1 as as the p70 S6 kinase; mTOR in The proteins eIF-4E BP1 and p70 S6 kinase each undergo an insulin/mitogen-stimulated phosphorylation in situ that is partially inhibited by rapamycin. Previous work has established that the protein known as mTOR/RAFT-1/FRAP is the target through which the rapamycin·FKBP12 complex acts to dephosphorylate/deactivate the p70 S6 kinase; thus, some mTOR mutants that have lost the ability to bind to the rapamycin·FKBP12 complex in vitro can protect the p70 S6 kinase against rapamycin-induced dephosphorylation/deactivationin situ. We show herein that such mTOR mutants also protect eIF-4E BP1 against rapamycin-induced dephosphorylation, and for both p70 S6 kinase and eIF-4E BP1, such protection that the mTOR an mutants p70 S6 kinase to by in situ to protect eIF-4E BP1 rapamycin-induced We that mTOR is an eIF-4E BP1 as as the p70 S6 kinase; mTOR in is an is the protein to to the by the and both in situ as through the through The complex by protein The rapamycin·FKBP12 complex and in situ the p70 S6 kinase an for the to in some in and the target rapamycin·FKBP12 in situ to the the p70 S6 kinase is the protein known as proteins in is The proteins the that to rapamycin-induced as The and proteins and mTOR that protein kinase to the protein kinase and the and and to the The complex to and the that in situ in The as the target for p70 S6 kinase has established by the work that p70 which the ability to bind to the rapamycin-induced that the BP1 is to the and eIF-4E to The eIF-4E the and the protein the the phosphorylation eIF-4E BP1 in the can phosphorylation eIF-4E BP1 is inhibited by as is for the is that the in by eIF-4E BP1 phosphorylation The the eIF-4E BP1 in situ is eIF-4E BP1 is by protein kinase in the eIF-4E BP1 eIF-4E BP1 is for the p70 S6 kinase in the p70 S6 kinase and the phosphorylation eIF-4E BP1 in to We is the that eIF-4E BP1 and to eIF-4E BP1 through the p70 We as mTOR the ability to the phosphorylation eIF-4E in p70 to eIF-4E BP1 phosphorylation by rapamycin. 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