3-Phosphoinositide dependent protein kinase 1 (PDK1) pleckstrin homology (PH) domain
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. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.
Jiyao W et al.(2023). "The conserved domain database in 2023.",