AGC protein kinase family (AGC)

The AGC protein kinase family is a large and diverse group of serine/threonine kinases named after its core members: Protein Kinase A (PKA), Protein Kinase G (PKG), and Protein Kinase C (PKC). This family encompasses over 60 human kinases, including critical signaling nodes such as AKT, p70S6K, SGK, and the Rho-associated kinases (ROCK) [1][2]. These enzymes are characterized by a conserved catalytic domain and a unique C-terminal extension known as the AGC-kinase C-terminal tail, which contains a hydrophobic motif essential for their phosphorylation and activation [3]. AGC kinases function as vital transducers of extracellular signals, regulating fundamental cellular processes including growth, metabolism, survival, and motility [1]. The term "Other AGC kinases" is often used in kinome classification to refer to family members like DMPK, GRK, and ROCK that fall outside the primary PKA/PKG/PKC subfamilies [2]. Dysregulation of AGC kinase signaling is a hallmark of numerous pathologies, including oncogenesis, metabolic disorders, and cardiovascular diseases [3]. Consequently, they are major targets in drug discovery, with several inhibitors approved for conditions ranging from glaucoma (e.g., Netarsudil) to various cancers (e.g., Capivasertib) [4][5][6]. (Citations: [1] Pearce et al., 2010, Nat Rev Mol Cell Biol; [2] Manning et al., 2002, Science; [3] Arencibia et al., 2013, Carcinogenesis; [4] FDA Label for Rhopressa; [5] FDA Label for Truqap; [6] Antman et al., 2023, NEJM).

Other names

Other AGC kinasesPKA, PKG, and PKC-like kinasesAGC groupAGC kinases

Inhibition of catalytic activity by competing with ATP for the binding site or through allosteric modulation of the hydrophobic motif in the C-terminal tail.