Linked Life Data

17991427

Source:http://linkedlifedata.com/resource/pubmed/id/17991427

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-12-6
pubmed:abstractText
Class IA phosphatidylinositol 3-kinase (PI 3-kinase), which is composed of a 110kDa catalytic subunit and a regulatory subunit, plays a key role in most insulin dependent cellular responses. To date, five mammalian regulatory subunit isoforms have been identified, including two 85kDa proteins (p85alpha and p85beta), two 55kDa proteins (p55gamma and p55alpha), and one 50kDa protein (p50alpha). In the present study, we overexpressed these recombinant proteins, tagged with green fluorescent proteins (GFP), in CHO-IR cells and investigated intracellular localizations in both the presence and the absence of insulin stimulation. Interestingly, in response to insulin, only p85alpha and p85beta redistributed to isolated foci in the cells, while both were present throughout the cytoplasm in quiescent cells. In contrast, p55s accumulated in the perinuclear region irrespective of insulin stimulation, while p50alpha behaved similarly to control GFP. Immunofluorescent antibodies against endogenous IRS-1 revealed IRS-1 to be co-localized in the p85 foci in response to insulin. As both insulin receptors and p110alpha catalytic subunits were absent from these foci on immunofluorescence study, only p85 and IRS-1 were suggested to form a sequestration complex in response to insulin. To determine the domain responsible for IRS-1 complex formation, we prepared and overexpressed the SH3 domain deletion mutant of p85alpha in CHO-IR cells. This mutant failed to form foci, suggesting the SH3 domain of regulatory subunits to be responsible for formation of the p85-IRS-1 sequestration complex. In conclusion, our study revealed the SH3 domain of PI 3-kinase to play a critical role in intracellular localizations, including formation of foci with IRS-1 in response to insulin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
365
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
433-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
SH3 domain of the phosphatidylinositol 3-kinase regulatory subunit is responsible for the formation of a sequestration complex with insulin receptor substrate-1.
pubmed:affiliation
Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical University, Morohongo 38, Moroyama, Iruma-gun, Saitama 350-0495, Japan.
pubmed:publicationType
Journal Article