Dephosphorylation and inactivation of Akt after detachment from Hsp90.
(A) 293T cells were transfected with the FLAG-tagged
WT-akt. After transfection for 24 h, cells were
cultured in the medium containing no serum (−) or 10% FBS (+) for
24 h. Then, the FLAG-tagged Akt was immunoprecipitated and
immunoblotted with the indicated antibodies. (B) The
HA-tagged akt mutants, the V5-tagged
WT-hsp90β, and/or the FLAG-tagged
WT-akt were cotransfected into 293T cells. The cells
were serum-starved for 24 h, and then FLAG-tagged WT-Akt was
immunoprecipitated and immunoblotted with the indicated antibodies. The
cell lysates were also immunoblotted with the indicated antibodies.
(C) 293T cells were transfected with mock or the
FLAG-tagged WT-akt together with mock or the HA-tagged
1–309 akt. The cells were serum-starved for 24 h
and then harvested. The cell lysates were incubated with protein G
agarose conjugated with a control IgG (lane 1) or an anti-Akt pAb
(lanes 2 and 3). The Akt kinase activity of the immunoprecipitated Akt
was estimated, as described in Materials and Methods.
The vertical bars represent SD value of triplicate determinations. The
immunoprecipitated proteins and the cell lysates were immunoblotted
with the indicated antibodies. (D) HT1080 cells were
transfected with the FLAG-tagged WT-akt together with
V5-tagged WT-hsp90β. The cells were serum-starved for
24 h and then incubated at 37°C or 45°C for 20 min. In some
experiments, cells were treated with 50 μM LY294002 for 10 min before
heat shock. The Akt kinase activity of the immunoprecipitated
FLAG-tagged Akt was estimated, as described in Materials and
Methods. The vertical bars represent SD value of triplicate
determinations. The cell lysates were also immunoblotted with the
indicated antibodies. (E) HT1080 cells were transfected
with the FLAG-tagged WT-akt, and the V5-tagged
WT-hsp90β together with mock or the HA-tagged 1–309
akt. The cells were serum-starved for 24 h and then
incubated at 37°C (−) or 45°C (+) for 20 min. The
immunoprecipitated FLAG-tagged WT-Akt and the cell lysates were
immunoblotted with the indicated antibodies. The expression of the
HA-tagged 1–309 Akt was confirmed by immunoblot analysis with an
anti-HA mAb (data not shown). Molecular size markers are indicated
(in kDa).