Nature 358, 242 - 245 (16 July 1992); doi:10.1038/358242a0

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

Alberto M. Martelli^*, R. Stewart Gilmour^†, Valeria Bertagnolo^‡, Luca M. Neri^‡§, Lucia Manzoli & Lucio Cocco^*¶

Institutes of Human Anatomy at the Universities of ^* Bologna, V. Irnerio, 48, 40126, ^‡ Ferrara, V. Fossato di Mortara, 66, 44100 and Chieti, V. dei Vestini, 66013, Bologna, Italy ^§ Institute of Cytomorphology, Consiglio Nazionale delle Ricerche, c/o Istituto Rizzoli, Bologna 40136, Italy ^† Department of Molecular and Cellular Physiology, AFRC, Institute of Animal Physiology and Genetics Research, Babraham, Cambridge CB2 4AT, UK ^¶ To whom correspondence should be addressed.

THE hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP₂) 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 PtdInsP₂and phosphatidylinositol 4-phosphate (PtdlnsP) in vitro¹and 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 diacylglycerol⁴ 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 lipids⁷. A key question is how IGF-1 initiates the rapid breakdown of PtdlnsP and PtdlnsP², in the nucleus. Here we present evidence that nuclei of 3T3 cells contain the -isozyme of phosphoinositidase C, whereas the -isozyme is confined to the cytoplasm and that IGF-1 treatment stimulates exclusively the activity of nuclear phosphoinositidase C.

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