PKGs are cyclic GMP-dependent protein kinases (also designed cGKs) that are classified into two types, PKGI and PKGII. Studies have shown that cGKs and cyclic AMP-dependent kinases (cAKs) are highly homologous protein kinase families with similar substrate specificities. Phosphorylation of cellular proteins by both families of kinases leads to alterations in calcium mobilization, protein phosphatase activity, ion channel function, gene transcription, smooth muscle contractility and platelet aggregation. However, recent studies using mice deficient in PKGs have shown that cGMP kinases regulate very specifically distinct pathways which are separate from those used by cyclic AMP kinases.