title: Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration.
abstract: The lipid products of phosphoinositide 3-kinase (PI3K) are involved in many cellular responses such as proliferation, migration, and survival. Disregulation of PI3K-activated pathways is implicated in different diseases including cancer and diabetes. Among the three classes of PI3Ks, class I is the best characterized, whereas class II has received increasing attention only recently and the precise role of these isoforms is unclear. Similarly, the role of phosphatidylinositol-3-phosphate (PtdIns-3-P) as an intracellular second messenger is only just beginning to be appreciated. Here, we show that lysophosphatidic acid (LPA) stimulates the production of PtdIns-3-P through activation of a class II PI3K (PI3K-C2beta). Both PtdIns-3-P and PI3K-C2beta are involved in LPA-mediated cell migration. This study is the first identification of PtdIns-3-P and PI3K-C2beta as downstream effectors in LPA signaling and demonstration of an intracellular role for a class II PI3K. Defining this novel PI3K-C2beta-PtdIns-3-P signaling pathway may help clarify the process of cell migration and may shed new light on PI3K-mediated intracellular events.
authors.affiliation: Department of Medicine, The Sackler Institute, University College London, London WC1E 6JJ, England, UK.
authors.forename: Tania
authors.initials: T
authors.lastname: Maffucci
authors.forename: Frank T
authors.initials: FT
authors.lastname: Cooke
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Foster
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Traer
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fry
authors.forename: Marco
authors.initials: M
authors.lastname: Falasca
mesh_terms: D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002521:Cercopithecus; D058541:Class II Phosphatidylinositol 3-Kinases; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D058541:Class II Phosphatidylinositol 3-Kinases; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases; C502616:PIK3C2B protein, human; C061816:phosphatidylinositol-3-phosphatase; C032881:lysophosphatidic acid