Nuclear localization and signalling activity of phosphoinositidase Cβ in Swiss 3T3 cells

• Published in: Nature (London) 1992-07, Vol.358 (6383), p.242-245
• Main Authors: Martelli, Alberto M., Gilmour, R. Stewart, Bertagnolo, Valeria, Neri, Luca M., Manzoli, Lucia, Cocco, Lucio
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Biological and medical sciences; Cell Nucleus - enzymology; Cell physiology; Cellular biology; Chromatography, High Pressure Liquid; Cytoplasm - enzymology; Enzymes; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Immunohistochemistry; Inositol Phosphates - isolation & purification; Inositol Phosphates - metabolism; Insulin-Like Growth Factor I - pharmacology; Isoenzymes - analysis; Isoenzymes - isolation & purification; Isoenzymes - metabolism; Kinetics; letter; Lipids; Mice; Molecular and cellular biology; multidisciplinary; Phosphoric Diester Hydrolases - analysis; Phosphoric Diester Hydrolases - isolation & purification; Phosphoric Diester Hydrolases - metabolism; Science; Signal Transduction; Translocation
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/358242a0

THE hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP 2 ) is a widespread receptor-coupled signalling system at the plasma membrane of most eukaryotic cells. The existence of an entirely separate nuclear phosphoinositide signalling system is suggested from evidence that purified nuclei synthesize PtdInsP 2 and phosphatidylinositol 4-phosphate (PtdlnsP) in vitro 1 and that a transient decrease in the mass of these lipids occurs when Swiss 3T3 cells are cultured in the presence of insulin-like growth factor-1 (IGF-1) 2–4 . These IGF-1-dependent changes in inositol lipids coincide with an increase in nuclear diacylglycerol 4 and precede translocation to the nucleus and activation of protein kinase C (refs 5, 6). Circumstantial evidence that links these changes with mitosis comes from the isolation of a 3T3 clone that expresses the type-1 IGF receptor and binds IGF-1 peptide but does not respond mitogenically or show transient mass changes in nuclear inositol lipids 7 . A key question is how IGF-1 initiates the rapid breakdown of PtdlnsP and PtdlnsP 2 , in the nucleus. Here we present evidence that nuclei of 3T3 cells contain the β-isozyme of phosphoinositidase C, whereas the γ-isozyme is confined to the cytoplasm and that IGF-1 treatment stimulates exclusively the activity of nuclear phosphoinositidase C.