Phosphorylation of intracellular proteins is a key biochemial mechanism by which many extracellular hormones exert their effects on cellular function. In many instances, calcium ions or cyclic nucleotides (cyclic AMP and cyclic GMP) act as intracellular intermediaries between hormone binding and activation of phosphorylation. Surprisingly, although much work has been done on protein phosphorylation mechanisms in the retina, little is known about the regulation of phosphorylation in the ciliary process and lens, including its epithelium. Hormone receptors (beta-adrenergic, prostaglandin, steroid, parathyroid hormone) are present in these two tissues, and preliminary work (including data from this laboratory) indicates the existence of endogenous protein substrates that are phosphorylated by cyclic-nucleotide-dependent protein kinases. We propose to investigate, in the lens, lens capsule and ciliary process, the regulation of protein phosphorylation by cyclic nucleotides, calcium and various hormones. Using both intact tissue and broken cell preparations, endogenous protein substrates for phosphorylation will be identified and characterized, along with the phosphorylating (kinases) and dephosphorylating (phosphatases) enzymes. In the ciliary process, phosphorylation in the epithelium, itself, will be studied using epithelial cell isolation techniques. Particular emphasis will be put on the hormone regulation of phosphorylation using prelabeling and back-phosphorylation techniques. These studies should provide an improved understanding of how hormones and ions regulate these tissues. In the ciliary process, such regulation is relevant to the physiology of aqueous humor secretion (with relevance to glaucoma) and, in the lens epitheliun, to the maintenance of lens metabolism (with relevance to cataract formation).

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005077-04
Application #
3259819
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-12-01
Project End
1987-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Ellis, D Z; Nathanson, J A; Rabe, J et al. (2001) Carbachol and nitric oxide inhibition of Na,K-ATPase activity in bovine ciliary processes. Invest Ophthalmol Vis Sci 42:2625-31