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Cyclic guanosine monophosphate-dependent protein kinase type II (PKG II)
- Target
- PKG II
- Molecular classification
- Enzyme, Kinase, Serine/threonine protein kinase, Membrane-bound kinase, Member of the AGC kinase family
01
Overview
Cyclic guanosine monophosphate-dependent protein kinase type II (PKG II) is a membrane-bound serine/threonine kinase encoded by the PRKG2 gene that is selectively activated by cGMP. It regulates bone growth via ERK activation, controls electrolyte and water secretion in intestinal and renal tissues, and plays a role in neuronal functions such as memory formation. It is structurally distinct from PKG I, with reversed positions of cGMP-binding domains and membrane association via N-terminal myristoylation[2][3][4][6]. PKG II acts as a tumor suppressor in some contexts and is a therapeutic target for diseases linked to impaired cGMP signaling such as certain cancers, cardiovascular diseases, and bone growth disorders[4][6][8].
- Other names
- Protein kinase G type IIPKG IIcGK IIPRKG2 (gene name)cGMP-dependent protein kinase II
02
Mechanism of action
Drugs increase intracellular cGMP, activating PKG II, which phosphorylates target proteins to regulate cellular functions
03
Biological functions
Signal transductionRegulation of bone growthRenin and aldosterone secretionRegulation of electrolyte and water secretionAdjustment of biological clockMemory formation and neuronal plasticityCell proliferation, apoptosis, migration, differentiation
04
Disease associations
Cancer (tumor suppressor functions, anti-proliferative effects)Cardiovascular disease (hypertensive heart disease, pulmonary hypertension)Osteoporosis (bone growth regulation)Chronic painSecretory diarrheas (intestinal secretion dysfunction)Others: possible roles in inflammation and neurodegenerative disease
05
Safety considerations
Potential risk of off-target effects due to broad tissue distributionExcessive activation in intestine may induce diarrheaEffects on bone growth and electrolyte balance need monitoring
06
Interacting drugs
No approved drugs specifically targeting PKG II as primary mechanism, but PKG pathway is targeted by drugs modulating cGMP levels such as phosphodiesterase inhibitors
1 more in the full profile.
07
Biomarkers
PRKG2 mRNA/protein expression (for tissue or tumor profiling)Phosphorylation status of downstream effectors such as ERK, RhoA (for pathway activity)cGMP levels (for efficacy of drugs affecting the pathway)
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