Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-3-25
pubmed:abstractText
The atypical protein kinase C (PKC) isotypes (lambda/iotaPKC and zetaPKC) have been shown to be critically involved in important cell functions such as proliferation and survival. Previous studies have demonstrated that the atypical PKCs are stimulated by tumor necrosis factor alpha (TNF-alpha) and are required for the activation of NF-kappaB by this cytokine through a mechanism that most probably involves the phosphorylation of IkappaB. The inability of these PKC isotypes to directly phosphorylate IkappaB led to the hypothesis that zetaPKC may use a putative IkappaB kinase to functionally inactivate IkappaB. Recently several groups have molecularly characterized and cloned two IkappaB kinases (IKKalpha and IKKbeta) which phosphorylate the residues in the IkappaB molecule that serve to target it for ubiquitination and degradation. In this study we have addressed the possibility that different PKCs may control NF-kappaB through the activation of the IKKs. We report here that alphaPKC as well as the atypical PKCs bind to the IKKs in vitro and in vivo. In addition, overexpression of zetaPKC positively modulates IKKbeta activity but not that of IKKalpha, whereas the transfection of a zetaPKC dominant negative mutant severely impairs the activation of IKKbeta but not IKKalpha in TNF-alpha-stimulated cells. We also show that cell stimulation with phorbol 12-myristate 13-acetate activates IKKbeta, which is entirely dependent on the activity of alphaPKC but not that of the atypical isoforms. In contrast, the inhibition of alphaPKC does not affect the activation of IKKbeta by TNF-alpha. Interestingly, recombinant active zetaPKC and alphaPKC are able to stimulate in vitro the activity of IKKbeta but not that of IKKalpha. In addition, evidence is presented here that recombinant zetaPKC directly phosphorylates IKKbeta in vitro, involving Ser177 and Ser181. Collectively, these results demonstrate a critical role for the PKC isoforms in the NF-kappaB pathway at the level of IKKbeta activation and IkappaB degradation.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-2665943, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-7590248, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-7673165, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-7744003, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-7867060, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8011280, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8026469, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8034680, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8336714, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8423794, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8523529, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8524286, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8557035, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8612133, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8622692, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8663336, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8717528, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8898208, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-8995387, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9008162, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9020361, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9244310, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9252183, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9252186, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9294162, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9312025, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9342307, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9346241, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9346484, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9346485, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9363938, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9447975, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9452444, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9520401, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9520446, http://linkedlifedata.com/resource/pubmed/commentcorrection/10022904-9529147
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CHUK protein, human, http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase, http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human, http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Mitogens, http://linkedlifedata.com/resource/pubmed/chemical/PRKCA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C lambda, http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C zeta
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0270-7306
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2180-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Activation of IkappaB kinase beta by protein kinase C isoforms.
pubmed:affiliation
Laboratorio Glaxo Wellcome-CSIC de Biología Molecular y Celular, Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Universidad Autónoma, 28049 Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't