PKG

cGMP-dependent protein kinase (PKG) is the main executor of nitric oxide and natriuretic peptide signaling. cGMP produced by NO-sensitive soluble or particulate guanylyl cyclases activates PKG I, a soluble homodimer existing as alpha and beta splice variants, and PKG II, which is membrane-anchored by myristoylation. The kinase phosphorylates substrates such as vasodilator-stimulated phosphoprotein (VASP), IRAG, and the myosin-light-chain phosphatase targeting subunit, lowering calcium sensitivity and relaxing smooth muscle. Consequently PKG governs vascular tone and blood pressure, platelet inhibition, and intestinal fluid secretion. Its mechanism underlies the therapeutic action of NO donors, natriuretic peptides, and PDE5 inhibitors, and the kinase is pursued in pulmonary hypertension and fibrosis programs. Recombinant PKG supports cyclic-nucleotide research and cardiovascular drug discovery.