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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000871-29
Application #
6125160
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Mariani, Andrew P
Project Start
1995-02-01
Project End
2001-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
29
Fiscal Year
2000
Total Cost
$346,385
Indirect Cost
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
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