InterPro domain: IPR033931

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 [ 1 ]. 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. [ 2 , 3 , 4 , 5 ].

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 [ 6 , 7 , 8 ].

1. Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates. EMBO J. 23, 3918-28
2. Mutation of the PDK1 PH domain inhibits protein kinase B/Akt, leading to small size and insulin resistance. Mol. Cell. Biol. 28, 3258-72
3. Phosphoinositide-dependent protein kinase 1, a sensor of protein conformation. Trends Biochem. Sci. 29, 136-42
4. The PI3K-PDK1 connection: more than just a road to PKB. Biochem. J. 346 Pt 3, 561-76
5. 3'-phosphoinositide-dependent kinase-1 (PDK-1) in PI 3-kinase signaling. Front. Biosci. 7, d886-902
6. Membrane targeting by pleckstrin homology domains. Curr. Top. Microbiol. Immunol. 282, 49-88
7. Phosphoinositide recognition domains. Traffic 4, 201-13
8. A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae. Mol. Syst. Biol. 6, 430