|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
12
|
|
pubmed:dateCreated |
2009-3-16
|
|
pubmed:abstractText |
The regulation of lipid homeostasis by insulin is mediated in part by the enhanced transcription of the gene encoding SREBP-1c (sterol regulatory element-binding protein-1c). Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c. There is limited indirect evidence to suggest that insulin may also regulate the posttranslational processing of the nascent SREBP-1c protein. Therefore, we designed experiments to directly assess the action of insulin on the post-translational processing of epitope-tagged full-length SREBP-1c and SREBP-2 proteins expressed in cultured hepatocytes. We demonstrate that insulin treatment led to enhanced post-translational processing of SREBP-1c, which was associated with phosphorylation of ER-bound nascent SREBP-1c protein that increased affinity of the SREBP-1c cleavage-activating protein (SCAP)-SREBP-1c complex for the Sec23/24 proteins of the COPII vesicles. Furthermore, chemical and molecular inhibitors of the phosphoinositide 3-kinase pathway and its downstream kinase protein kinase B (PKB)/Akt prevented both insulin-mediated phosphorylation of nascent SREBP-1c protein and its posttranslational processing. Insulin had no effect on the proteolysis of nascent SREBP-2 under identical conditions. We also show that in vitro incubation of an active PKB/Akt enzyme with recombinant full-length SREBP-1c led to its phosphorylation. Thus, insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins and subsequent ER to Golgi transport and proteolytic cleavage. This effect of insulin is tightly linked to phosphoinositide 3-kinase and PKB/Akt-dependent serine phosphorylation of the precursor SREBP-1c protein.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-10207099,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-10500120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-10514488,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-10535992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-10570128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-10861205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-10947952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-11001944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-11111080,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-11734577,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-11994399,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-12031952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-12242332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-12624180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-12963821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-14505487,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-14633850,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-15330762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-15576458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-15637161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-15772151,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-15896314,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-15899885,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-16054087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-16413480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-16493415,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-16679292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-17449871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-17666007,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-18291668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-6828386,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-7637810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-7759101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-7774014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-7862668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-8175660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-8202496,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-8276779,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-8922375,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-9062340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-9150132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-9428766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-9498625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-9531548,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19158095-9600904
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
20
|
|
pubmed:volume |
284
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
7518-32
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
|
