title: Phosphatidylserine binding is essential for plasma membrane recruitment and signaling function of 3-phosphoinositide-dependent kinase-1.
abstract: 3-Phosphoinositide-dependent kinase-1 (PDK1) is a ubiquitously expressed serine/threonine kinase that functions downstream of phosphoinositide 3-kinase. Although binding of 3'-phosphoinositides, phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate, to the pleckstrin homology (PH) domain of PDK1 is known to be essential for its interaction with and activation of downstream kinases, the mechanism by which PDK1 is recruited to the plasma membrane remains controversial. Our surface plasmon resonance analysis of the PDK1 PH domain and selected mutants shows that the PH domain specifically binds phosphatidylserine using a site that is separate from the canonical phosphoinositide-binding site. Further cell studies show that this specific phosphatidylserine binding is important for the plasma membrane localization and signaling function of PDK1.
authors.affiliation: Department of Chemistry, University of Illinois, Chicago, Illinois 60607.
authors.forename: Nathan
authors.initials: N
authors.lastname: Lucas
authors.affiliation: Department of Chemistry, University of Illinois, Chicago, Illinois 60607. Electronic address: wcho@uic.edu.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Cho
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000235:genetics / Q000378:metabolism; D010718:Phosphatidylserines / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C000631433:Pdk1 protein, mouse