Protein kinase C-ζ-induced phosphorylation of Ser318 in insulin receptor substrate-1 (IRS-1) attenuates the interaction with the insulin receptor and the tyrosine …
K Moeschel, A Beck, C Weigert, R Lammers… - Journal of Biological …, 2004 - ASBMB
Insulin receptor substrate-1 (IRS-1) was recently identified as a novel upstream substrate for
the insulin-activated protein kinase C (PKC)-ζ. This interaction down-regulates insulin signal
transduction under hyper-insulinemic conditions. To clarify the molecular mechanism of this
feedback loop, we sought to identify the PKC-ζ phosphorylation sites of IRS-1 and to
investigate their biological significance. Upon incubation of recombinant IRS-1 fragments
with PKC-ζ, we identified Ser 318 of rat IRS-1 (Ser 323 in human IRS-1) as the major in vitro …
the insulin-activated protein kinase C (PKC)-ζ. This interaction down-regulates insulin signal
transduction under hyper-insulinemic conditions. To clarify the molecular mechanism of this
feedback loop, we sought to identify the PKC-ζ phosphorylation sites of IRS-1 and to
investigate their biological significance. Upon incubation of recombinant IRS-1 fragments
with PKC-ζ, we identified Ser 318 of rat IRS-1 (Ser 323 in human IRS-1) as the major in vitro …
