Abstracts
1999 Digestive Disease Week

# 2130 A NOVEL CLASS II PHOSPHOINOSITIDE 3-KINASE PREDOMINANTLY EXPRESSED IN THE LIVER AND ITS ENHANCED EXPRESSION DURING LIVER REGENERATION
fuminori ono, masanori suzuki, michiaki unno, hisatake kondo, seiki matsuno, tohoku Univ Sch of Medicine, sendai Japan

Phosphoinositide 3-kinase (PI 3-kinase) catalyzes the phosphorylation of phosphoinositides such as phosphatidylinositol (PtdIns), PtdIns 4-P and PtdIns 4,5-P2 at the D3 position of the inositol ring to generate PtdIns 3-P, PtdIns 3,4-P2 and PtdIns 3,4,5-P3, respectively. Earlier studies focused on the role of PI 3-kinases in growth factor-stimulated and tyrosine kinase receptor-mediated cascades, but recent studies support the involvement of this lipid kinase in inhibition of apoptosis, intracellular vesicle trafficking and regulation of cytoskeletal functions in addition to mitogenic signaling Since initial identification of the molecular structure of PI 3-kinase, cDNA cloning analyses have revealed multiple catalytic subunits of this kinase family which can now be classified into three classes on the basis of their structural characteristics and in vitro lipid substrate specificity. We report herein the cloning and characterization of a novel class II phosphoinositide 3-kinase, termed PI3K-IIÉg, from the cDNA library of regenerating rat liver. This cDNA encodes a protein of 1505 amino acids with a calculated molecular weight of 170,972 Da. The amino acid sequence of PI3K-IIÉg 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-IIÉg displays a restricted substrate-specificity for PtdIns and PtdIns 4-P, but not for PtdIns 4,5P2. By epitope tag immunocytochemistry, the immunoreactivity for PI3K-IIÉg 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-IIÉg 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-IIÉg may function mainly in highly differentiated hepatic cells.

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