Cytoplasmic–nuclear shuttling of FRAP regulates downstream signaling.
Myc-tagged FRAP proteins with various translocation signals were
coexpressed with HA-p70s6k or FLAG-4E-BP1 in HEK293 cells.
Various FRAP proteins are designated as follows: WT, wild-type; NLS,
NLS-FRAP; NLS′, NLS′-FRAP; NES, NES-FRAP; NES′, NES′-FRAP; KD,
kinase-dead. All FRAP constructs, including wild type, contained the
S2035T mutation. All cells were pretreated with 100 nM rapamycin for 30
min before serum stimulation for 1 h. LMB treatment was carried
out for 12 h before lysis. (A) In
vitro kinase assays were performed with immunoprecipitated
HA-p70s6k. Results are shown as activities relative to that
for wild type. Expressions of Myc-FRAP and HA-p70s6k were
monitored by Western blotting, by using epitope tag antibodies.
(B) Phosphorylation of FLAG-4E-BP1 as reflected by
mobility shift was examined by Western blotting, using M2 anti-FLAG
antibody.