Despite advancement in the treatment and understanding of the pathogenesis leading to heart failure, the cellular and molecular mechanisms involved are still largely unknown. Left ventricular hypertrophy is a common feature associated with the heart failure state, and may be associated with reduced contractile function. Therefore, the overall goal of this proposal is to determine the signal transduction pathways leading to cardiac hypertrophy. Several researchers have demonstrated that treatment of cultured NRVM with hypertrophic agonists leads to activation of the family of MAP kinases including ERK1/2, JNK1/2, and p38. PYK2, a non-receptor tyrosine kinase activated by Ca2+ influx and PKC, has been implicated as an important kinase linking the activation of G protein-coupled receptors to the activation of ERK and JNK in other cell types. The present research proposal is designed to test the hypothesis that the calcium-dependent non-receptor tyrosine kinase PYK2 plays a critical role in the generation of the hypertrophic phenotype in cardiac myocytes.
The Specific Aims of this proposal are 1) to evaluate the expression of PYK2 in cardiac myocytes 2) to determine the role(s) of PYK2 in activation of the MAP kinase cascades. Understanding the receptors and signaling pathways associated with the development of cardiac hypertrophy, such as alterations in gene expression, may result in the discovery of novel therapeutic targets for the treatment of heart failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL010313-01
Application #
6056157
Study Section
Special Emphasis Panel (ZRG1-HEM-2 (01))
Project Start
2000-02-01
Project End
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
1
Fiscal Year
2000
Total Cost
$32,416
Indirect Cost
Name
Loyola University Chicago
Department
Type
Schools of Medicine
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153
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