Protein kinase N1 (PKN1)

Protein kinase N kinases (PKN1, PKN2, and PKN3) are AGC-family serine/threonine protein kinases and effectors of the Rho family of small G proteins. These kinases play central roles in cell signaling pathways regulating actin cytoskeletal dynamics, cell migration, cell cycle progression, chromatin remodeling, cell adhesion, androgen receptor signaling, the immune response, and glucose metabolism. PKN1 and PKN2 are ubiquitously expressed, while PKN3 is expressed at lower levels in most tissues but higher in metastatic cancers. Activation of PKNs involves phosphorylation by PDK1 and interactions with Rho/Rac-family GTPases. Their dysregulation is implicated in various diseases, notably cancer, cardiovascular diseases, and some infections, marking them as promising yet understudied therapeutic targets. Isoform-specific targeting and understanding remain challenges for drug development and safety.

Other names

PRK1PRK2PRK3protein kinase C-related kinase 1/2/3protein kinase PKprotein kinase C-like 1protease-activated kinase 1

ATP-competitive inhibition (most kinase inhibitors), Induced degradation (e.g., PROTACs), Blockade of activation loop phosphorylation