The binding of insulin to its receptor initiates multiple signal trans
duction pathways regulating such diverse processes as proliferation, d
ifferentiation, glucose transport, and glycogen metabolism, The STAT-f
amily of transcription factors has been demonstrated to play a critica
l role in gene induction by a variety of hemopoietic cytokines and hor
mones, Furthermore, constitutive activation of STATs is observed in tr
ansformed cells, Here we describe activation of a transcriptional comp
lex binding to a consensus STAT-transcriptional element in response to
insulin challenge, This complex is induced rapidly after tyrosine aut
ophosphorylation of the insulin receptor, and is sustained for several
hours, Supershift analysis of the insulin-induced complex reveals tha
t it specifically contains the transcription factor Stat3, DAN binding
of this complex is inhibited by pre-incubation with tyrosine, but not
serine/threonine protein kinase inhibitors, whereas transcriptional a
ctivation is inhibited by both, Utilising a dominant negative mutant o
f p21ras we demonstrate that both insulin-induced Stat3 DNA-binding an
d also transactivation do not require p21ras, Furthermore, although pr
evious studies have suggested a role for MAP kinases (ERKs) and PI-3K
in STAT activation, utilising the specific MEK inhibitor PD098059 and
the PI-3K inhibitor wortmannin, we demonstrate that activation of ERKs
or PI-3K are not required for insulin induced Stat3 phosphorylation o
r transactivation.