InterPro domain: IPR039046

This family includes 3-phosphoinositide-dependent protein kinase 1 (PDK1 or PDPK1) and related kinases from yeast: Pkh1 and Pkh2 from S. cerevisiae, which function similarly to PDK1 [ 1 ], and Ksg1 [ 2 ] and Ppk21 from S. pombe [ 3 ].

PDK1 is the kinase responsible for the phosphorylation of PKB/Akt on the activation loop, at threonine 308, which is essential for Akt activation [ 4 , 5 ]. Beyond Akt, PDK1 is responsible for the phosphorylation of many other AGC kinases including serum/glucocorticoid regulated kinase (SGK) [ 6 ] and the members of protein kinase C (PKC) family [ 7 ]. PDK1 is implicated in signaling pathways frequently altered in cancer, such as PI3K/Akt, Ras/MAPK and Myc [ 8 ]. It is a key regulator of cell migration and tumor invasion [ 9 ]. PDK1 binds to the insulin receptor, followed by tyrosine phosphorylation of PDK1 by the insulin receptor, which is necessary for insulin metabolic signaling [ 10 ]. Deficiency of PDK1 in liver results in glucose intolerance [ 11 ].

1. Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. Curr. Biol. 9, 186-97
2. Ksg1, a homologue of the phosphoinositide-dependent protein kinase 1, controls cell wall integrity in Schizosaccharomyces pombe. J. Basic Microbiol. 43, 473-82
3. Roles of Pdk1p, a fission yeast protein related to phosphoinositide-dependent protein kinase, in the regulation of mitosis and cytokinesis. Mol. Biol. Cell 16, 3162-75
4. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr. Biol. 7, 261-9
5. Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1. Biochem. J. 337 ( Pt 3), 575-83
6. Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. Biochem. J. 339 ( Pt 2), 27168-76
7. Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. Science 281, 1-17
8. PDK1: At the crossroad of cancer signaling pathways. Semin. Cancer Biol. 48, 707-10
9. Serine/Threonine Kinase 3-Phosphoinositide-Dependent Protein Kinase-1 (PDK1) as a Key Regulator of Cell Migration and Cancer Dissemination. Cancers (Basel) 9, 27-35
10. Tyrosine phosphorylation of phosphoinositide-dependent kinase 1 by the insulin receptor is necessary for insulin metabolic signaling. Mol. Cell. Biol. 25, 639-48
11. Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure. Biochem. J. 385