Different properties of monomer and heterodimer forms of phosphatidyliglositol 3-kinases

Abstract

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). 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 K(i) values of 4 μM and 2.5 μM respectively. PI 3-kinase II, but not PI 3-kinase I, co-immunoprecipitates with pp60(v-src) and polyoma middle T (mT)/pp60(c-src) even under conditions where the PI 3-kinases are not phosphorylated, suggesting that non-phosphorylated PI 3-kinase recognizes autophosphorylated pp60(v-src). PI 3-kinase II is phosphorylated by pp60(v-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 pp60(v-src) in src-transformed cells, suggesting that PI 3-kinase II binds to pp60(v-src) in vivo. These data suggest that the two PI 3-kinases may be regulated independently.