Abstract

This is a competitive renewal proposal from an established investigator to continue his previous work analyzing the role of the RIIbeta protein kinase A gene product in the regulation of body weight and metabolism. During the previous funded period the PI demonstrated that genetically ablating RIIbeta resulted in mice which were lean and resisted diet-induced obesity. The proposed studies would clarify the mechanisms mediating these effects, by examining the role of UCP-1 in mediating the lean phenotype of RIIbeta knockouts, assessing the role of RIIbeta in specific tissues, determining the role of high-affinity scaffolding proteins in mediating effects of RIIbeta, and determining the role of PKA activity in mediating effects of the RIIbeta knockout.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032875-18
Application #
6489984
Study Section
Endocrinology Study Section (END)
Program Officer
Jones, Warren
Project Start
1983-12-01
Project End
2004-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
18
Fiscal Year
2002
Total Cost
$304,992
Indirect Cost

  Institution

Name
University of Washington
Department
Pharmacology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Flippo, Kyle H; Gnanasekaran, Aswini; Perkins, Guy A et al. (2018) AKAP1 Protects from Cerebral Ischemic Stroke by Inhibiting Drp1-Dependent Mitochondrial Fission. J Neurosci 38:8233-8242
Li, Lei; Li, Jing; Drum, Benjamin M et al. (2017) Loss of AKAP150 promotes pathological remodelling and heart failure propensity by disrupting calcium cycling and contractile reserve. Cardiovasc Res 113:147-159
Jones, Brian W; Deem, Jennifer; Younts, Thomas J et al. (2016) Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination. Elife 5:
Riggle, Kevin M; Riehle, Kimberly J; Kenerson, Heidi L et al. (2016) Enhanced cAMP-stimulated protein kinase A activity in human fibrolamellar hepatocellular carcinoma. Pediatr Res 80:110-8
Yang, Haihua; Yang, Linghai (2016) Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy. J Mol Endocrinol 57:R93-R108
Gilbert, Merle L; Yang, Linghai; Su, Thomas et al. (2015) Expression of a dominant negative PKA mutation in the kidney elicits a diabetes insipidus phenotype. Am J Physiol Renal Physiol 308:F627-38
Sanz, Elisenda; Quintana, Albert; Deem, Jennifer D et al. (2015) Fertility-regulating Kiss1 neurons arise from hypothalamic POMC-expressing progenitors. J Neurosci 35:5549-56
Yang, Linghai; McKnight, G Stanley (2015) Hypothalamic PKA regulates leptin sensitivity and adiposity. Nat Commun 6:8237
Yang, Linghai; Gilbert, Merle L; Zheng, Ruimao et al. (2014) Selective expression of a dominant-negative type I? PKA regulatory subunit in striatal medium spiny neurons impairs gene expression and leads to reduced feeding and locomotor activity. J Neurosci 34:4896-904
Vulto-van Silfhout, Anneke T; Rajamanickam, Shivakumar; Jensik, Philip J et al. (2014) Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems. Am J Hum Genet 94:649-61

Showing the most recent 10 out of 84 publications