Abstract

The goal of this research is to determine the physiological functions of PKA in vivo and assign specific roles to each of the 6 subunit genes in signal transduction. During the previous grant period, the principal investigator produced targeted mutations in each of the PKA subunits.
The aims of the next grant period are to utilize these gene knockout mice in physiological and biochemical studies and to make further mutations in the PKA system. Specific goals are to determine the physiological and developmental changes which occur as a result of the Ca knockout, to characterize the tissue-specific expression and function of recently discovered C beta splice variants, to determine the role of RIa in embryonic development, to measure the physiological defects in fat metabolism in RIIbeta mutant mice, to characterize the role of PKA isozymes in neuronal gene induction, and to examine the functional significance of PKA anchoring. It is anticipated that mice carrying """"""""genetic diseases"""""""" in the PKA pathway will provide a novel approach to understanding the physiological significance of the highly conserved PKA signaling system in mammals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032875-16
Application #
6018594
Study Section
Endocrinology Study Section (END)
Project Start
1983-12-01
Project End
2001-01-04
Budget Start
1999-09-30
Budget End
2001-01-04
Support Year
16
Fiscal Year
1999
Total Cost
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
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
Jones, Brian W; Deem, Jennifer; Younts, Thomas J et al. (2016) Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination. Elife 5:
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