Linked Life Data

9092546

Source:http://linkedlifedata.com/resource/pubmed/id/9092546

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1997-5-15
pubmed:abstractText
We have utilized the yeast two-hybrid system to identify proteins that interact with the cytoplasmic domain of the insulin receptor (IR). We identified a human cDNA encoding a protein that appears to be the human homolog of the yeast MAD2 protein, which we term hMAD2. The yeast MAD2 protein was first identified in a genetic screen to identify cell cycle checkpoint regulatory proteins, yet the mechanism by which MAD2 functions in cell cycle control is currently unclear. Here we show that hMAD2 requires the COOH-terminal 30 amino acids of the IR for interaction and that hMAD2 does not interact with the related insulin-like growth factor I receptor. Interestingly, hMAD2 does not require IR tyrosine autophosphorylation for interaction because it interacts with a kinase-dead IR in the yeast two-hybrid system. In support of this finding, hMAD2-GST fusions were found to interact strongly in vitro with receptors derived from noninsulin-stimulated cells. Furthermore, using two independent in vitro assays, IR activation was found to significantly reduce the interaction of hMAD2 with the IR. Lastly, we show that hMAD2 can be coimmunoprecipitated with the IR from Chinese hamster ovary IR cell lysates, suggesting that this interaction occurs in vivo in cells of mammalian origin. Our results suggest that hMAD2 represents a novel class of proteins that is specific for interaction with the IR as compared with the insulin-like growth factor I receptor and that interacts best with the inactive IR and is released upon receptor autophosphorylation. The function of hMAD2 and its potential role in insulin signaling remain to be elucidated.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10035-40
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Interaction of MAD2 with the carboxyl terminus of the insulin receptor but not with the IGFIR. Evidence for release from the insulin receptor after activation.
pubmed:affiliation
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't