cGMP-dependent protein kinase (PKG)

cGMP-dependent protein kinase (PKG) is a serine/threonine kinase that is the principal intracellular receptor for the signaling molecule cyclic GMP (cGMP)[1][3][4]. Upon binding cGMP, PKG phosphorylates multiple target proteins, regulating vascular smooth muscle tone, heart function, platelet activity, memory formation, apoptosis, ion channel conductance, and gene expression[1][4][6][9]. There are two major PKG isoforms: PKG-I (cytoplasmic) and PKG-II (membrane-associated), each with tissue-specific roles[7][5]. Disorders involving the cGMP-PKG pathway include heart failure, hypertension, erectile dysfunction, cancer, and certain neurodegenerative diseases[2][3][5][6][8]. Therapeutic agents such as PDE5 inhibitors and sGC stimulators, which modulate this pathway, have shown clinical benefit in several conditions[5][2]. The pathway’s complexity and broad therapeutic potential have made PKG a focal point for research in intracellular signaling, pharmacology, and disease modulation.

Other names

Protein kinase GPKGcGMP-dependent protein kinase IPKG-IcGMP-dependent protein kinase IIPKG-II

Elevation of intracellular cGMP increases PKG activity, resulting in phosphorylation of downstream proteins. PKG activation leads to muscle relaxation, apoptosis induction, inhibition of hypertrophy, modulation of cellular gene expression, and other effects depending on tissue context.