PKG1

cGMP-dependent protein kinase I (PKG1), encoded by the PRKG1 gene, is a key mediator in the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP signaling pathway, regulating diverse physiological processes including smooth muscle relaxation, platelet aggregation, and cardiac function^[1]. PKG1 exists as two major isoforms, PKG1α and PKG1β, arising from alternative splicing; while both share a catalytic domain, they differ significantly in their regulatory domains, leading to distinct subcellular localization and functional roles. PKG1α is predominantly cytosolic and involved in acute responses to cGMP elevation, whereas PKG1β exhibits nuclear localization and plays critical roles in transcriptional regulation and cell survival^[2]. Dysregulation of PKG1 signaling has been implicated in cardiovascular diseases such as hypertension, pulmonary arterial hypertension, and heart failure, with evidence showing reduced PKG1 activity in diseased tissues. Experimental models using PKG1 knockout mice reveal impaired vasodilation and increased vascular stiffness, underscoring its role in vascular homeostasis. Common agonists include 8-Br-cGMP and YC-1, while inhibitors like DT-2 and Rp-8-Br-PET-cGMPS are used to probe PKG1-specific functions. These tools have enabled research into therapeutic strategies targeting the NO/sGC/cGMP-PKG axis for treating cardiovascular and metabolic disorders^[3].