Phosphorylation of Mdm2. (a) Western blot analysis of
insulin receptor (control, 2 μg), Akt, and Mdm2 (2 μg)
immunoprecipitated from serum-starved MCF-7 cells probed with anti-Mdm2
(IF-2) or anti-Akt. (b) Serum-starved MCF-7 cells were
stimulated with 50 ng/ml IGF-1 and a Western blot was probed with
anti-phospho (activated)-Akt (Upper). The blot was
stripped and reprobed with anti-Akt (Lower).
(c) Serum-starved MCF-7 cells were treated with medium
or LY294002 for 30 min and then IGF-1 for 30 min. Western blots were
probed with anti-phospho Akt (Upper) or anti-Akt
(Lower). (d) MCF-7 cells were stimulated
with insulin before immunoprecipitation of Mdm2. A Western blot was
probed with anti-Akt and anti-Mdm2. (e) Recombinant Mdm2
or 2xSA was incubated with GST or GST-Akt-agarose for 30 min in
vitro, centrifuged, and washed three times. Vehicle or raAkt
was incubated with the agarose complexes for 30 min at 37°C and these
were centrifuged and washed three times. A Western blot probed with
anti-Mdm2 or anti-Akt quantitated the amount of Mdm2 or 2xSA that had
associated with GST-Akt agarose. (f) Mdm2
immunoprecipitated from MCF-7 cells incubated with vehicle or IGF-1 was
analyzed by mass spectrometry. Predicted parent ions for
unphosphorylated serine 166 and serine 186 were recovered from the
control incubates (Left), whereas parent ions predicted
for phosphorylated serine 166 and serine 186 were recovered from cells
treated with IGF-1 (Right).