Sathyamangla Prasad Laboratory

Research

Beta-adrenergic receptors (beta-ARs) belong to a family of seven transmembrane receptors, also known as the G-protein coupled receptors (GPCRs), that form the interface between the sympathetic nervous system and the cardiovascular system. Beta-ARs are one of the most powerful regulators of cardiac function that are chronically desensitized and downregulated in conditions of heart failure, in part, due to increased phosphorylation of beta-ARs by beta-adrenergic receptor kinase 1 (beta-ARK1). Beta-ARK1 forms a cytosolic complex with phosphoinositide 3-kinase (PI3K) and targets PI3K to the receptor complex following agonist stimulation. Beta-ARK1 targeted PI3K activity at the receptor complex is required for beta-AR internalizaton, as expression of inactive PI3K attenuates receptor internalization. Importantly, cardiac-specific overexpression of inactive PI3K ameliorates cardiac dysfunction in mouse models of heart failure by blocking the receptor of internalization, which seems to result in the preservation of beta-AR function. The underlying mechanism by which preservation of beta-AR function occurs is currently unknown. Identifying the mechanism by which PI3K regulates these protein(s) involved in the preservation of beta-AR function would allow us to develop novel therapeutic interventions for heart failure, or alternatively, could complement the current treatments. We are using a combination of proteomics, transgenic mouse models, and cell culture systems to comprehensively investigate and elucidate the underlying molecular mechanism.

Selected Publications

1. Mohan, M. L., Jha, B.K., Gupta, M.K., Vasudevan, N.T., Martelli, E.E., Mosinski, J.D., Naga Prasad, S.V.  (2013).  Phosphoinositide 3-Kinase g inhibits cardiac GSK-3 Independent of Akt.  Science Signaling 6(259):ra4 (Cover page article).
2. Mohan, M.L., Vasudevan, N.T., Gupta, M. K., Martelli, E.E. and Naga Prasad, S.V. (2012). G-protein coupled receptor resensitization – appreciating the balancing act of receptor function. Current Molecular Pharmacology, 5: 317-401.
3. Vasudevan, N.T., Mohan, M.L., Goswami, S.K. and Naga Prasad, S.V. (2011).  Regulation of b- Adrenergic receptor function:  An emphasis on receptor resensitization.  Cell Cycle, 10 (21): 3684-3691.
4. Vasudevan, N.T., Mohan, M.L., Gupta, M.K., Hussain, A. and Naga Prasad, S.V. (2011).  Inhibition of protein phosphatase 2A activity by PI3Kg regulates beta-adrenergic receptor function.  Mol. Cell, 41 (6): 636-648.