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 [], and Ksg1 []and Ppk21 from S. pombe [].PDK1 is the kinase responsible for the phosphorylation of PKB/Akt on the activation loop, at threonine 308, which is essential for Akt activation [, ]. Beyond Akt, PDK1 is responsible for the phosphorylation of many other AGC kinases including serum/glucocorticoid regulated kinase (SGK) []and the members of protein kinase C (PKC) family []. PDK1 is implicated in signaling pathways frequently altered in cancer, such as PI3K/Akt, Ras/MAPK and Myc []. It is a key regulator of cell migration and tumor invasion []. PDK1 binds to the insulin receptor, followed by tyrosine phosphorylation of PDK1 by the insulin receptor, which is necessary for insulin metabolic signaling []. Deficiency of PDK1 in liver results in glucose intolerance [].
This entry represents the pleckstrin homology (PH) domain from 3-phosphoinositide-dependent protein kinase 1 (PDK1) type proteins.PDK1 plays an important role in insulin and growth factor signalling cascades. It phosphorylates and activates many AGC (cAMP-dependent, cGMP-dependent, protein kinase C (PKC)) family of protein kinases members, including protein kinase B (PKB, also known as Akt), p70 ribosomal S6-kinase (S6K), serum and glucocorticoid responsive kinase (SGK), p90 ribosomal S6 kinase (RSK), and PKC []. PDK1 contains an N-terminal serine/threonine kinase domain followed by a PH domain. Following binding of the PH domain to PtdIns(3,4,5)P3 and PtdIns(3,4)P2, PDK1 activates these enzymes by phosphorylating a Ser/Thr residue in their activation loop. [, , , ].Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of signalling proteins, where they serve as simple targeting domains that bind lipids [, , ].
