Extracellular signal-control elevations in intracellular Ca2+ levels regulate a diverse array of cellular phenomena. Evidence has accumulated for calcium dyshomeostatsis in nervous system pathologies including HIV-induced neuronal injury, Alzheimer's disease and Parkinson's disease suggesting the potential for new pharmacological interventions for these disorders based on alteration in intracellular Ca2+ levels. Calcium calmodulin (CaM) dependent protein kinases (CaM kinase) are important mediators of the effects of elevated levels of intracellular calcium upon physiologically relevant target proteins. CaM kinase I is the focus of this proposal. This research is intended to provide an integrated approach for elucidating the signaling cascade for phosphorylation and activation of CaM kinase I.
The specific aims are: 1. Identification of extracellular and intracellular signals which induce phosphorylation and activation of CaM kinase I in pheochromocytoma PC12 cells; 2, Analysis of signal transduction mechanisms in the CaM kinase I cascade. Specifically to determine by immunoprecipitation techniques if CaM kinase I (or CaM kinase IV) forms complexes with its activating kinases (CaMKIKs) and evaluate whether phosphorylation of CaMKIKs influence their abilities to phosphorylate and activate CaM kinase I and to form complexes with CaM kinase I.; 3. Evaluation of the respective roles of CaMKIKs in CaM kinase cascades. Specifically to determine through studies of their respective kinetics of phosphorylation whether CaMKIKs utilize CaM kinase I preferentially as substrate relative to CaM kinase IV and determine their respective localization using Northern and immunoblotting and immunocytochemistry, and whether the CaMkKIKs have cell type or tissue specific functions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024738-10
Application #
2635694
Study Section
Neurology C Study Section (NEUC)
Program Officer
Baughman, Robert W
Project Start
1988-02-01
Project End
1999-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Pharmacology
Type
Schools of Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260