A novel class II phosphoinositide 3-kinase predominantly expressed in the liver and its enhanced expression during liver regeneration

We report herein the cloning and characterization of a novel class II phosphoinositide 3-kinase, termed PI3K-IIγ, from the cDNA library of regenerating rat liver. This cDNA encodes a protein of 1505 amino acids with a calculated molecular mass of 170,972 Da. The amino acid sequence of PI3K- IIγ is highly similar to those of class II PI 3-kinases, including murine Cpk-m/p170 and human HsC2-PI3K. It contains a C2 domain at the C terminus but no recognizable protein motifs at its N terminus. PI3K-IIγ displays a restricted substrate specificity for PtdIns and PtdIns 4-P, but not for PtdIns 4,5-P₂. By epitope tag immunocytochemistry, the immunoreactivity for PI3K-IIγ is localized in the juxtanuclear Golgi region at high levels and also in the plasma and nuclear membranes at low levels. By Northern blot analysis and in situ hybridization histochemistry, PI3K-IIγ mRNA expression is confined to the liver throughout the development with much higher expression in adult liver than in fetal liver. In addition, its expression increases during liver regeneration after partial hepatectomy with maximal expression after the growth period, suggesting that PI3K-IIγ may function mainly in highly differentiated hepatic cells.