Abnormal Morphogenesis But Intact IKK Activation in Mice Lacking the IKK
Subunit of I
B Kinase
Yinling Hu,
1
Véronique Baud,
1*
Mireille Delhase,
1*
Peilin Zhang,
2
Thomas Deerinck,
3
Mark Ellisman,
3
Randall Johnson,
4
Michael Karin
1
The oligomeric I
B kinase (IKK) is composed of three
polypeptides: IKK
and IKK
, the catalytic subunits, and IKK
, a
regulatory subunit. IKK and IKK are similar in structure and
thought to have similar function--phosphorylation of the
IB inhibitors in response to proinflammatory stimuli. Such
phosphorylation leads to degradation of IB and
activation of nuclear factor B transcription factors. The
physiological function of these protein kinases was explored by
analysis of IKK-deficient mice. IKK was not required for
activation of IKK and degradation of IB by proinflammatory stimuli.
Instead, loss of IKK interfered with multiple morphogenetic events,
including limb and skeletal patterning and proliferation and
differentiation of epidermal keratinocytes.
1 Laboratory of Gene Regulation and Signal
Transduction, Department of Pharmacology, and
2 Departments of Pathology,
3 Neuroscience, and
4 Biology,
Cancer Center, University of California San Diego, La Jolla, CA
92093-0636, USA.
*
These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail:
karinoffice{at}ucsd.edu
