TNF inhibits tyrosine phosphorylation of IRS-1 and activates Akt.
(A) Serum-starved NIH 3T3 fibroblasts were incubated
with medium, insulin (10 nM, 5 min), or TNF (10 nM) for various times
and then insulin. After immunoprecipitation (IP) of IRS-1 a Western
blot was probed with an antibody to phosphotyrosine and then with
anti-IRS-1 to demonstrate fractionation of equal amounts of protein
from cell lysates. (B) Serum-starved NIH 3T3 cells were
incubated with 10 nM TNF for 0–60 min (Upper) and 0–24
h (Lower). Cell lysates were fractionated on 10%
polyacrylamide gels and Western blots were probed with an antibody
directed against phospho-Akt (Upper), stripped, and
reprobed with an anti-Akt antibody (Lower).
(C) Serum-starved myotubes were incubated with 10 nM TNF
for various times before fractionation of proteins on a 7%
polyacrylamide gel. A Western blot was probed with anti-phospho-Akt
(Upper) and then with anti-Akt (Lower).