Biochemistry Commons^™

Exploring The Mechanisms Of Pkg1-Α Activation By Synthetic Peptides, Connor Cronin

Graduate College Dissertations and Theses

Cyclic GMP-dependent protein kinases (PKG’s) are essential signaling macromolecules which play a pivotal role in vascular physiology and smooth muscle tone regulation. As principle downstream effectors of the secondary messenger cyclic 3’, 5’-guanosine-monophosphate (cGMP), PKG isoforms are expressed in high levels in all types of smooth muscle cells. The broad range of cellular functions effected by PKG include platelet aggregation, hypertrophy, apoptosis, neuronal plasticity, gene expression, differentiation, vasorelaxation, vascular remodeling, calcium homeostasis, and cardiac function. Recently, a newly characterized helical switch domain within the alpha isoform of PKG (PKG1-α) has led to the development of S1.1, a novel cGMP-independent peptide …

The A-Site In The Pkg Iα Regulatory Domain Controls Both Cgmp- And Oxidative-Dependent Activation, Jessica Lynne Sheehe

Graduate College Dissertations and Theses

The type Iα cGMP-dependent protein kinase (PKG Iα) is an essential regulator of vascular tone and systemic blood pressure. Located in the smooth muscle of resistance vessels, PKG Iα stimulates vasodilation through the phosphorylation of multiple intracellular substrates. Its primary regulator is the small molecule, 3',5'-cyclic guanosine monophosphate (cGMP); however, the Iα isoform can also be activated by oxidation. Despite the established physiological importance of PKG Iα, the structural underpinnings of these two activation mechanisms are largely unknown.

The work presented in this dissertation demonstrates the importance of the cGMP-binding domain A (CBD-A) in regulating both of these mechanisms of …