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Molecular targets and role in heart disease treatment

PKG is the effecter kinase of cyclic GMP, the latter generated by either nitric oxide or natriuretic peptide stimulated guanylyl cyclases. In the vasculature, PKG is prominently involved with vasomotor tone, but is also protective against oxidant and other disease stressors.  Our laboratory focuses on the role of PKG in the heart where it imparts protective effects against pathologic pressure-load, ischemic, and other cardiotoxic stresses.  Until recently little was known about which proteins are engaged by activated PKG that protect the heart against disease stress. We have now revealed critical interactions with regulator of G-signaling proteins, the cation channel TRPC6, the proteasome, and most recently with tuberous sclerosis complex protein 2 (TSC2) that modulates the mechanistic target of rapamycin. These impact growth, fibrosis, protein quality control, autophagy, and other signaling pathways. The work is translational and is leading to novel heart disease therapeutics.

Protein Kinase G: Project
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