Different properties of monomer and heterodimer forms of phosphatidylinositol 3-kinases.
Phosphatidylinositol (PI) 3-kinase plays an important role in the signalling of cell growth. We previously purified two types of PI 3-kinase from bovine thymus, a monomer from (PI 3-kinase I) and a heterodimer form (PI 3-kinase II) [Shibasaki, Homma and Takenawa (1991) J. Biol. Chem. 266, 8108-8114]. Here we examine the properties of these purified PI 3-kinases. Both PI 3-kinases were inhibited strongly by quercetin and isoquercetin. The inhibition of PI 3-kinase I and PI 3-kinase II by quercetin appears to be non-competitive, with apparent Ki values of 4 microM and 2.5 microM respectively. PI 3-kinase II, but not PI 3-kinase I, co-immunoprecipitates with pp60v-src and polyoma middle T (mT)/pp60c-src, even under conditions where the PI 3-kinases are not phosphorylated, suggesting that non-phosphorylated PI 3-kinase recognizes autophosphorylated pp60v-src. PI 3-kinase II is phosphorylated by pp60v-src and binds to it. Anti-p85 (85 kDa subunit of PI 3-kinase II) antibody precipitates not only PI 3-kinase II but also co-immunoprecipitates pp60v-src in src-transformed cells, suggesting that PI 3-kinase II binds to pp60v-src in vivo. These data suggest that the two PI 3-kinases may be regulated independently.
Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Japan.
F
F
Shibasaki
Y
Y
Fukui
T
T
Takenawa
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002461:Cell Line, Transformed; D004277:DNA, Single-Stranded; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000494:pharmacology; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D010743:Phospholipids / Q000494:pharmacology; D010766:Phosphorylation; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D051381:Rats
D004277:DNA, Single-Stranded; D009711:Nucleotides; D010743:Phospholipids; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D015688:Oncogene Protein pp60(v-src)