title: The alpha-isoform of class II phosphoinositide 3-kinase is more effectively activated by insulin receptors than IGF receptors, and activation requires receptor NPEY motifs.
abstract: Little is known about the physiological role and mechanism of activation of class II phosphoinositide 3-kinases (PI3Ks), although it has been shown that the PI3K-C2alpha isoform is activated by insulin. Using chimaeric receptor constructs which can be activated independently of endogenous receptors in transfected cells, we found that PI3K-C2alpha activity was stimulated to a greater extent by insulin receptors than IGF receptors in 3T3-L1 adipocytes. Activation of PI3K-C2alpha required an intact NPEY motif in the receptor juxtamembrane domain. We conclude that PI3K-C2alpha is a candidate for participation in insulin-specific intracellular signalling.
authors.affiliation: University of Cambridge, Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: B
authors.initials: B
authors.lastname: Ursø
authors.forename: R A
authors.initials: RA
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: P R
authors.initials: PR
authors.lastname: Shepherd
authors.forename: K
authors.initials: K
authors.lastname: Siddle
mesh_terms: D016475:3T3 Cells / Q000201:enzymology; D017667:Adipocytes / Q000201:enzymology; D020816:Amino Acid Motifs / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D051379:Mice; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D010649:Phenylalanine / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014443:Tyrosine / Q000235:genetics
chemical_list: D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D010649:Phenylalanine; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin