Abstract

Activation of a variety of cell surface receptors leads the activation of PLC and the subsequent hydrolysis of plasma membrane phospholipid, phosphatidylinositol bis-phosphate (PIP2). The two products of PIP2 hydrolysis, inositol-3-phosphate (IP3) and diacylglycerol (DAG), are second messengers involved in the regulation of cellular Ca2+ and protein kinase C (PKC) activities. PIP2 is also a substrate of a PI-3 kinase. The product of this PI-3 kinase, phosphatidylinositol tris-phosphate (PIP3), appears to be an important second messenger for a distinct cellular pathway. Vertebrate photoreceptor outer segments contain light-sensitive PLC, PKC, and an active PI-3 kinase. In this proposal, the applicant proposes experiments to define the role of PLC and PI-3 kinase. There are 3 specific aims: (1) identification of the light-sensitive PLC in rod outer segments (ROS) and elucidation of its mechanism of activation; (2) investigation of the enzymes in the PI cycle that replenish PIP2 in photoreceptor; and (3) determination of the role of PI-3 kinase in the retina.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000871-28
Application #
2838244
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1995-02-01
Project End
2001-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
28
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Oklahoma Health Sciences Center
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117

  Publications

Rajala, Raju V S; Rajala, Ammaji (2018) Redundant and Nonredundant Functions of Akt Isoforms in the Retina. Adv Exp Med Biol 1074:585-591
Rajala, Ammaji; Wang, Yuhong; Brush, Richard S et al. (2018) Pyruvate kinase M2 regulates photoreceptor structure, function, and viability. Cell Death Dis 9:240
Rajala, Ammaji; Wang, Yuhong; Rajala, Raju V S (2018) Constitutive Activation Mutant mTOR Promote Cone Survival in Retinitis Pigmentosa Mice. Adv Exp Med Biol 1074:491-497
Wang, Yuhong; Rajala, Ammaji; Rajala, Raju V S (2018) Nanoparticles as Delivery Vehicles for the Treatment of Retinal Degenerative Diseases. Adv Exp Med Biol 1074:117-123
Agbaga, Martin-Paul; Merriman, Dana K; Brush, Richard S et al. (2018) Differential composition of DHA and very-long-chain PUFAs in rod and cone photoreceptors. J Lipid Res 59:1586-1596
Hopiavuori, Blake R; Deák, Ferenc; Wilkerson, Joseph L et al. (2018) Homozygous Expression of Mutant ELOVL4 Leads to Seizures and Death in a Novel Animal Model of Very Long-Chain Fatty Acid Deficiency. Mol Neurobiol 55:1795-1813
Hopiavuori, Blake R; Agbaga, Martin-Paul; Brush, Richard S et al. (2017) Regional changes in CNS and retinal glycerophospholipid profiles with age: a molecular blueprint. J Lipid Res 58:668-680
Rajala, Ammaji; Wang, Yuhong; Rajala, Raju V S (2016) Activation of oncogenic tyrosine kinase signaling promotes insulin receptor-mediated cone photoreceptor survival. Oncotarget 7:46924-46942
Rajala, Raju V S; Rajala, Ammaji; Kooker, Christopher et al. (2016) The Warburg Effect Mediator Pyruvate Kinase M2 Expression and Regulation in the Retina. Sci Rep 6:37727
Azadi, Seifollah; Brush, Richard S; Anderson, Robert E et al. (2016) Class I Phosphoinositide 3-Kinase Exerts a Differential Role on Cell Survival and Cell Trafficking in Retina. Adv Exp Med Biol 854:363-9

Showing the most recent 10 out of 188 publications