The DED of PEA-15 is necessary but not sufficient
for PEA-15 activation of ERK. (A) Depiction of the PEA-15 mutant
constructs. The mutated aspartate (D74) is indicated, as are
phoshphorylated serines (S104, S116). All recombinant proteins are
fused to an HA tag. DD is structurally related to the DED. (B)
αβpy-Cells were cotransfected with expression vectors encoding
HA-ERK (2 μg) in combination with PEA-15 (4 μg), PEA-15-DED (DED; 8
μg), PEA-15-C-Term (C-Term; 8 μg), PEA-15(D74A) (4 μg), DD-PEA-15
(4 μg), or vector lacking insert (Control; 8 μg). Cell lysates were
analyzed by SDS-PAGE followed by immunoblotting. Top,
immunoblot with a polyclonal antibody specific for
phosphorylated active ERK1. Note that only wild-type PEA-15 activates
ERK. Middle and bottom, immunoblots with anti-HA antibody
12CA5. Note transfected HA-ERK expression levels are comparable in all
transfections. Bottom, note the expression of all PEA-15 constructs.
(C) αβpy-Cells were cotransfected with expression vectors encoding
HA-ERK (2 μg) in combination with PEA-15 (3 μg) or E8 (3 μg).
Cell lysates were analyzed by SDS-PAGE followed by
immunoblotting. Top, immunoblot with a
polyclonal antibody to phosphorylated ERK1/2 (phosphorylated HA-ERK is
shown). Note that E8 does not activate ERK. Middle,
immunoblot with anti-HA antibody. Bottom,
immunoblot with antimyc antibody.