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PMID: 15928202 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration.

The Journal of cell biology ·Vol. 169 ·No. 5 ·2005-06-06 ·Pages 789-99

Maffucci T, Cooke FT, Foster FM, Traer CJ, Fry MJ, Falasca M

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.

MeSH Terms
Animals COS Cells Cell Movement/drug effects,physiology Cercopithecus Class II Phosphatidylinositol 3-Kinases Enzyme Activation/drug effects,physiology Enzyme Inhibitors/pharmacology HeLa Cells Humans Lysophospholipids/metabolism,pharmacology Phosphatidylinositol 3-Kinases/metabolism Phosphoinositide-3 Kinase Inhibitors Phosphoric Monoester Hydrolases/metabolism Signal Transduction/drug effects,physiology Wound Healing/drug effects,physiology
Chemicals
Enzyme Inhibitors Lysophospholipids Phosphoinositide-3 Kinase Inhibitors Class II Phosphatidylinositol 3-Kinases PIK3C2B protein, human Phosphoric Monoester Hydrolases phosphatidylinositol-3-phosphatase lysophosphatidic acid
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Maffucci Tania
Department of Medicine, The Sackler Institute, University College London, London WC1E 6JJ, England, UK.
Cooke Frank T
Foster Fiona M
Traer Colin J
Fry Michael J
Falasca Marco
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200408005
Published
2005-06-06
Epub
2005-00-31
Pages
789-99
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171608
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1083/jcb.200408005 PMC Full Text View journal details
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