Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinase.
The oligomeric IkappaB kinase (IKK) is composed of three polypeptides: IKKalpha and IKKbeta, the catalytic subunits, and IKKgamma, a regulatory subunit. IKKalpha and IKKbeta are similar in structure and thought to have similar function-phosphorylation of the IkappaB inhibitors in response to proinflammatory stimuli. Such phosphorylation leads to degradation of IkappaB and activation of nuclear factor kappaB transcription factors. The physiological function of these protein kinases was explored by analysis of IKKalpha-deficient mice. IKKalpha was not required for activation of IKK and degradation of IkappaB by proinflammatory stimuli. Instead, loss of IKKalpha interfered with multiple morphogenetic events, including limb and skeletal patterning and proliferation and differentiation of epidermal keratinocytes.
Hu
Y
Y
Department of Pharmacology, Cancer Center, University of California San Diego, La Jolla, CA 92093-0636, USA.
Baud
V
V
Delhase
M
M
Zhang
P
P
Deerinck
T
T
Ellisman
M
M
Johnson
R
R
Karin
M
M
D000015:Abnormalities, Multiple / Q000201:enzymology / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D001842:Bone and Bones / Q000002:abnormalities / Q000196:embryology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D005314:Embryonic and Fetal Development; D004789:Enzyme Activation; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology; D005260:Female; D018390:Gene Targeting; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D015603:Keratinocytes; D017880:Limb Deformities, Congenital / Q000201:enzymology; D008297:Male; D051379:Mice; D009024:Morphogenesis; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000196:embryology; D012868:Skin Abnormalities / Q000201:enzymology
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse