http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-7485434-B2
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_0fc2a22a9271507062ad7e07974d3c58 |
| classificationCPCAdditional | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/G01N2500-00 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C12Q1-485 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P43-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/G01N33-6875 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/G01N33-5008 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/G01N33-5035 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/G01N33-5067 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/G01N33-507 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C12Q1-50 |
| filingDate | 2006-04-04-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| grantDate | 2009-02-03-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_7518361925fb218fe80e066eab25b139 |
| publicationDate | 2009-02-03-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | US-7485434-B2 |
| titleOfInvention | Method for screening compounds for those that modulate transducers of regulated CREB activity |
| abstract | In accordance with the present invention, it has been discovered that glucose and incretin hormones promote pancreatic islet cell survival via the calcium and cAMP dependent induction, respectively, of the transcription factor CREB. Specifically, a signaling module has been identified which mediates cooperative effects of calcium and cAMP on islet cell gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a cytoplasmic CREB coactivator. The module comprises a cAMP regulated snf1-like kinase called SIK2 and the calcium regulated phosphatase calcineurin, both of which associate with TORC2 in the cytoplasm. TORC2 is repressed under basal conditions through a phosphorylation dependent interaction with 14-3-3 proteins. cAMP and calcium signals stimulate CREB target gene expression via complementary effects on TORC2 dephosphorylation; cAMP disrupts TORC2-associated activity of SIK2 or related family members, whereas calcium induces TORC2 dephosphorylation via calcineurin. These findings provide a novel mechanism by which CREB activates cellular gene expression, depending on nutrient and energy status, and facilitate development of assays to identify compounds which modulate the role of TORCs. In accordance with the present invention, it has been discovered that fasting and energy-sensing pathways regulate the gluconeogenic program in liver by modulating the nuclear entry of a transcriptional coactivator called Transducer of Regulated CREB Activity 2 (TORC2). Hepatic TORC2 over-expression induces fasting hyperglycemia, whereas knockdown of TORC2 leads to fasting hypoglycemia and silencing of the gluconeogenic program. Since a majority of individuals with Type II diabetes exhibit fasting hyperglycemia due to elevated hepatic gluconeogenesis, compounds that enhance TORC2 phosphorylation will find use as therapeutic agents in this setting. |
| priorityDate | 2005-04-04-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 1533.