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As a member of AGC kinases family, PDK-1, a protein of 556 amino acids, is composed of serine and threonine kinases. The catalytic domain of these serine and threonine kinases show a sequential similarity with cAMP-dependent protein kinase 1 (PKA), cGMP-dependent protein kinase (PKG) and protein kinase C (PKC). There are two phosphorylation sites that many AGC kinases and they are to regulate the activity of AGC kinases.
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PDK-1 Signaling Pathway As a member of AGC kinases family, PDK-1, a protein of 556 amino acids, is composed of serine and threonine kinases. The catalytic domain of these serine and threonine kinases show a sequential similarity with cAMP-dependent protein kinase 1 (PKA), cGMP-dependent protein kinase (PKG) and protein kinase C (PKC). There are two phosphorylation sites that many AGC kinases and they are to regulate the activity of AGC kinases. The one which is located within the kinase domain is called activation loop, while the other one named hydrophobic motif is located in a region which is adjacent to the catalytic domain. The enzymatic full activation is triggered by phosphorylation of activation loop and hydrophobic motif which is catalyzed by an autophosphorylation reaction. n addition, PDK-1 kinase also has a PH domain. The PH (3,4)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate that is essential in localization and activation of some of membrane associated PDK-1's substrates such as AKT. The kinase domain has three ligand binding sites, namely the substrate binding site, the ATP binding site, and the docking site which is also known as PIF pocket. The PIF pocket interacts and binds some PDK-1 substrates such as S6K and Protein kinase C . Several small molecule allosteric activators of PDK-1 in previous studies were shown to inhibit the activation of substrates selectively. Instead of binding to the active site, these small molecules enable PDK-1 to activate other substrates which do not require docking site interaction. So far, there is no well-defined inhibitor for PDK-1. One of the most important substrate of PDK-1 is AKT. The activation of AKT requires a proper orientation of the kinase and PH domains of PDK-1 and AKT at the membrane. Many proteins that interact with PDK-1 via a hydrophobic motif named PDK-1 interacting fragment (PIF). domain is used for mainly interacting with phosphatidylinositol https://www.creative-diagnostics.com/pdk-1-signaling-pathway.htm
