cGMP-dependent protein kinase 2 (PRKG2)

cGMP-dependent protein kinase 2 (PRKG2, also known as PKGII) is a membrane-anchored serine/threonine kinase that serves as a primary effector of cyclic guanosine monophosphate (cGMP) signaling in specific mammalian tissues [1, 4]. Unlike its cytosolic counterpart PKGI, PRKG2 is tethered to the plasma membrane via N-terminal myristoylation and is highly expressed in the intestinal mucosa, kidney, and chondrocytes [5, 7]. Its biological functions include the regulation of electrolyte and water secretion through the phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR), as well as the modulation of endochondral bone growth and renin secretion [1, 3, 14]. In disease, PRKG2 is a central mediator of secretory diarrhea triggered by bacterial heat-stable enterotoxins, and its genetic deficiency is linked to acromesomelic dysplasia, a form of severe short stature [1, 14]. Furthermore, it acts as a tumor suppressor in the colon by inhibiting cell proliferation and promoting differentiation [9]. While few direct clinical inhibitors are currently approved, PRKG2 is functionally targeted through the use of guanylate cyclase-C (GC-C) agonists like linaclotide, which increase cGMP levels to activate the enzyme for the treatment of gastrointestinal disorders [13, 15]. Experimental research also identifies PRKG2 as a potential neuroprotective target in achromatopsia to prevent cone photoreceptor degeneration [16].

Other names

cGMP-dependent protein kinase IIcGKIIPKGIIProtein kinase G IIcGK2

cGMP-mediated activation leading to the phosphorylation of specific substrates such as CFTR, SOX9, and GluA1 to regulate ion transport, gene expression, and synaptic strength