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[Cancer Research 54, 2536-2540, May 15, 1994]
© 1994 American Association for Cancer Research

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Phosphoinositide Signaling in Nuclei of Friend Cells: Phospholipase C ß Down-Regulation Is Related to Cell Differentiation1

Alberto M. Martelli, Anna M. Billi, R. Stewart Gilmour, Luca M. Neri, Lucia Manzoli, Andrea Ognibene and Lucio Cocco2

Department of Morphology, University of Trieste, Via Manzoni, 16, 34138 Trieste [A. M. M.], Institute of Anatomy, University of Bologna, Via Irnerio, 48, 40126 Bologna [A. M. B., L. C.], Institute of Anatomy, University of Ferrara, Via Fossato di Mortara, 66, 44100 Ferrara [L. M. N.], Institute of Anatomy, University of Chieti, Via dei Vestini, 66013 Chieti [L. M.], Institute of Cytomorphology, CNR [L. M. N.], and Laboratory for Electron Microscopy and Cell Biology IOR, Via di Barbiano 1/10, 40136 Bologna [A. O.], Italy, and Department of Molecular and Cellular Physiology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge CB2 4AT, United Kingdom [S. G.]

Previous investigations have demonstrated the existence of an autonomous intranuclear inositide cycle endowed with conventional lipid kinases and phospholipase C (PLC) which is the isoform ß in Swiss 3T3 cells, PC12 pheochromocytoma cells, human osteosarcoma SaOS-2 cells, and rat liver. The presence of PLC has been investigated in nuclei of Friend erythroleukemia cells. Both ß and {gamma} isoforms are present in these nuclei. When Friend cells undergo terminal erythroid differentiation in the presence of dimethyl sulfoxide the PLCß isoform is down-regulated as shown by immunochemical and immunocytochemical analysis, by determination of enzymatic activity directly and in the presence of neutralizing monoclonal antibodies and also by Northern blot for PLC ß message. By contrast, the amount of PLC{gamma} and its activity are unaffected by erythroid differentiation. Thus, the presence of a nuclear PLCß, the activity and expression of which are modulated during differentiation of erythroleukemia cells, implicates a role for nuclear phosphoinositide signaling in the processes of cell determination and indicates the nuclear PLCß as a key enzyme of the cycle in relation to the erythroid differentiative commitment of murine erythroleukemia cells.

1 This work was supported by Italian CNR Grants PF IG and PF ACRO and by the AFRC International Scientific Interchange Scheme.

2 To whom requests for reprints should be addressed.

Received 1/21/94. Accepted 4/ 5/94.




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Copyright © 1994 by the American Association for Cancer Research.