Involvement of PI3K in Stat3-dependent and -independent migration of
keratinocytes. (A) Costimulation with insulin and PMA
promoted appreciable migration of either wild-type (+/+, black bars)
or Stat3-disrupted (−/−, white bars) keratinocytes, either of which
did not migrate by insulin or PMA alone. Migration of both types of
cells was blocked by a PI3K inhibitor, wortmannin, in a dose-dependent
manner. *, P < 0.05; **,
P < 0.01 by Student's t test.
(B) Wortmannin (50 nM) blocked 60%, 56% of the
migration of wild-type cells promoted by EGF, HGF, respectively.
**, P < 0.01 by Student's
t test. (C) Western blot analyses
revealed that stimulation not only of Stat3+/+ but also of
Stat3−/− keratinocytes with HGF (50 ng/ml) or insulin
(25 μg/ml) resulted in phosphorylation of Akt, a direct target of
PI3K (16), indicating that PI3K activation in response to HGF or
insulin was not affected by Stat3 ablation.