Publication Date:
1999-04-09
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Y -- Baud, V -- Delhase, M -- Zhang, P -- Deerinck, T -- Ellisman, M -- Johnson, R -- Karin, M -- R01 AI43477/AI/NIAID NIH HHS/ -- R37 ES04151/ES/NIEHS NIH HHS/ -- RR04050/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):316-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Cancer Center, University of California San Diego, La Jolla, CA 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195896" target="_blank"〉PubMed〈/a〉
Keywords:
Abnormalities, Multiple/enzymology/genetics
;
Animals
;
Apoptosis
;
Body Patterning
;
Bone and Bones/abnormalities/embryology
;
Cell Differentiation
;
Cell Nucleus/metabolism
;
Cells, Cultured
;
DNA-Binding Proteins/metabolism
;
Dimerization
;
*Embryonic and Fetal Development
;
Enzyme Activation
;
Epidermis/cytology/embryology
;
Female
;
Gene Targeting
;
I-kappa B Kinase
;
I-kappa B Proteins
;
Keratinocytes
;
Limb Deformities, Congenital/enzymology
;
Male
;
Mice
;
*Morphogenesis
;
Mutation
;
Phosphorylation
;
Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism
;
Skin/embryology
;
Skin Abnormalities/enzymology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
