Linked Life Data

14522956

Source:http://linkedlifedata.com/resource/pubmed/id/14522956

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2003-12-8
pubmed:abstractText
Acrp30/adiponectin is an adipocyte-derived serum protein with important roles in regulation of lipid and glucose metabolism, but which of its isoforms are biologically active remains controversial. We addressed this issue by first characterizing the structure of each individual Acrp30 oligomer and the determinants responsible for multimer formation. Freeze etch electron microscopy showed the trimer to exhibit a ball-and- stick-like structure containing a large globular sphere, an extended collagen stalk, and a smaller sphere on the opposite end of the stalk. The hexamer consists of two adjacent trimeric globular domains and a single stalk composed of collagen domains from two trimers. Although not necessary for trimer formation or stability, two of the three monomers in an Acrp30 trimer are covalently linked by a disulfide bond between cysteine residues at position 22. In contrast, assembly of hexameric and higher molecular weight (HMW) forms of Acrp30 depends upon formation of Cys22-mediated disulfide bonds because their reduction with dithiothreitol or substitution of Cys22 with alanine led exclusively to trimers. HMW and hexamer isoforms of Acrp30 activated NF-kappaB in C2C12 cells, but trimers, either natural, formed by reduction of Acrp30 hexamer, or formed by the C22A mutant, did not. In contrast, incubation of isolated rat extensor digitorum longus with naturally formed Acrp30 trimers or trimeric C22A Acrp30 led to increased phosphorylation of AMP-activated protein kinase-alpha at Thr172 and its activation. Hexameric and HMW Acrp30 could not activate AMP-activated protein kinase. Thus, trimeric and HMW/hexameric Acrp30 activate different signal transduction pathways, and Acrp30 represents a novel example of the control of ligand signaling via changes in its oligomerization state.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
50810-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14522956-Adiponectin, pubmed-meshheading:14522956-Alanine, pubmed-meshheading:14522956-Amino Acid Sequence, pubmed-meshheading:14522956-Animals, pubmed-meshheading:14522956-Blotting, Western, pubmed-meshheading:14522956-Cell Line, pubmed-meshheading:14522956-Chromatography, Gel, pubmed-meshheading:14522956-Cryoelectron Microscopy, pubmed-meshheading:14522956-Cysteine, pubmed-meshheading:14522956-Dimerization, pubmed-meshheading:14522956-Disulfides, pubmed-meshheading:14522956-Dithiothreitol, pubmed-meshheading:14522956-Genes, Reporter, pubmed-meshheading:14522956-Humans, pubmed-meshheading:14522956-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:14522956-Ligands, pubmed-meshheading:14522956-Luciferases, pubmed-meshheading:14522956-Mice, pubmed-meshheading:14522956-Molecular Sequence Data, pubmed-meshheading:14522956-Muscles, pubmed-meshheading:14522956-Mutagenesis, Site-Directed, pubmed-meshheading:14522956-NF-kappa B, pubmed-meshheading:14522956-Protein Conformation, pubmed-meshheading:14522956-Protein Isoforms, pubmed-meshheading:14522956-Proteins, pubmed-meshheading:14522956-Sequence Homology, Amino Acid, pubmed-meshheading:14522956-Signal Transduction
pubmed:year
2003
pubmed:articleTitle
Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways.
pubmed:affiliation
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't