The extracellular matrix is connected to the intracellular cytoskeleton at focal adhesion sites via integrin transmembrane receptors. One tyrosine protein kinase which as been shown to be associated with integrin clustering is pp125FAK (FAK). The present research proposal is designed to test the hypothesis that the integrin-pp125FAK (FAK). The present research proposal is designed to test the hypothesis that the integrin-pp125FAK tyrosine protein kinase complex is the receptor responsible for lead dependent changes in cardiac gene expression.
The specific aims of this research are 1) to determine FAK protein, FAK phosphorylation, and FAK immunolocalization in contracting and quiescent cultured neonatal and adult ventricular myocytes and to correlate these data to mRNA levels of b-MHC, ANF, and SERCA2, 2) to determine whether the inhibition of FAK phosphorylation will affect the expression of these genes, and 3) to determine whether the activity of the ANF promoter can be modulated by either overexpressing FAK which has been shown to inhibit FAK phosphorylation. Understanding the mechanisms responsible for mechanochemical signal transduction in cardiac myocytes will allow for a better understanding of how the myocardium adapts or fails to adapt to an increased load.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL009611-03
Application #
2771202
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1998-09-01
Project End
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Loyola University Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153
Eble, D M; Strait, J B; Govindarajan, G et al. (2000) Endothelin-induced cardiac myocyte hypertrophy: role for focal adhesion kinase. Am J Physiol Heart Circ Physiol 278:H1695-707
Eble, D M; Spragia, M L; Ferguson, A G et al. (1999) Sarcomeric myosin heavy chain is degraded by the proteasome. Cell Tissue Res 296:541-8
Eble, D M; Walker, J D; Samarel, A M et al. (1998) Myosin heavy chain synthesis during the progression of chronic tachycardia induced heart failure in rabbits. Basic Res Cardiol 93:50-5
Eble, D M; Cadre, B M; Qi, M et al. (1998) Contractile activity modulates atrial natriuretic factor gene expression in neonatal rat ventricular myocytes. J Mol Cell Cardiol 30:55-60
Eble, D M; Qi, M; Waldschmidt, S et al. (1998) Contractile activity is required for sarcomeric assembly in phenylephrine-induced cardiac myocyte hypertrophy. Am J Physiol 274:C1226-37
Cadre, B M; Qi, M; Eble, D M et al. (1998) Cyclic stretch down-regulates calcium transporter gene expression in neonatal rat ventricular myocytes. J Mol Cell Cardiol 30:2247-59