Publication Date:
2002-02-16
Description:
Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole activation mechanism. Here, we report an unexpected activation mechanism for p38alpha MAPK that does not involve the prototypic kinase cascade. Rather it depends on interaction of p38alpha with TAB1 [transforming growth factor-beta-activated protein kinase 1 (TAK1)-binding protein 1] leading to autophosphorylation and activation of p38alpha. We detected formation of a TRAF6-TAB1-p38alpha complex and showed stimulus-specific TAB1-dependent and TAB1-independent p38alpha activation. These findings suggest that alternative activation pathways contribute to the biological responses of p38alpha to various stimuli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ge, Baoxue -- Gram, Hermann -- Di Padova, Franco -- Huang, Betty -- New, Liguo -- Ulevitch, Richard J -- Luo, Ying -- Han, Jiahuai -- AI41637/AI/NIAID NIH HHS/ -- HL07195/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Feb 15;295(5558):1291-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11847341" target="_blank"〉PubMed〈/a〉
Keywords:
*Adaptor Proteins, Signal Transducing
;
Binding Sites
;
Calcium-Calmodulin-Dependent Protein Kinases/metabolism
;
Carrier Proteins/chemistry/genetics/*metabolism
;
Cell Line
;
*Drosophila Proteins
;
Enzyme Activation
;
Enzyme Inhibitors/pharmacology
;
Humans
;
Imidazoles/pharmacology
;
*Intracellular Signaling Peptides and Proteins
;
MAP Kinase Kinase 6
;
*MAP Kinase Signaling System
;
Membrane Glycoproteins/metabolism
;
Mitogen-Activated Protein Kinase 14
;
Mitogen-Activated Protein Kinase Kinases/metabolism
;
Mitogen-Activated Protein Kinases/antagonists &
;
inhibitors/chemistry/genetics/*metabolism
;
Mutation
;
Peptide Mapping
;
Peroxynitrous Acid/pharmacology
;
Phosphorylation
;
Proteins/metabolism
;
Pyridines/pharmacology
;
Receptors, Cell Surface/metabolism
;
Recombinant Fusion Proteins/metabolism
;
TNF Receptor-Associated Factor 6
;
Toll-Like Receptors
;
Tumor Necrosis Factor-alpha/pharmacology
;
Two-Hybrid System Techniques
;
p38 Mitogen-Activated Protein Kinases
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
