title: Mitogen-stimulated events in nuclei of Swiss 3T3 cells. Evidence for a direct link between changes of inositol lipids, protein kinase C requirement and the onset of DNA synthesis.
abstract: Two different clones of Swiss 3T3 cells belonging to the same original cell line have been obtained, one of which was unresponsive to mitogenic stimulation (e.g. insulin-like growth factor-I, bombesin, insulin-like growth factor-I + bombesin), while the other clone showed a very high rate of DNA synthesis under identical conditions as demonstrated by 5-bromodeoxyuridine incorporation. Both types of cells expressed the IGF-I receptor and showed high contact inhibition. When highly purified nuclei from responsive cells, treated for a short time with bombesin and insulin-like growth factor-I or insulin-like growth factor-I alone, were incubated with [gamma-32P]adenosine triphosphate, the labelling of phosphatidylinositol-mono- and diphosphate decreased when compared to controls, while this transient effect did not appear in the nuclei from unresponsive cells. Similarly nuclear protein kinase C is activated only in responsive cells. Therefore, it seems that a direct link exists between polyphosphoinositide metabolism, protein kinase C activation and the early events leading to cell division, since the rapid changes in the labelling of both phosphatidylinositol mono- and di-phosphate occur only in nuclei from Swiss 3T3 cells, which respond to the mitogenic stimulus determined by insulin-like growth factor-I on its own, or in combination with bombesin.
authors.affiliation: Istituti di Anatomia Umana Normale, Università di Bologna, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Martelli
authors.forename: R S
authors.initials: RS
authors.lastname: Gilmour
authors.forename: L M
authors.initials: LM
authors.lastname: Neri
authors.forename: L
authors.initials: L
authors.lastname: Manzoli
authors.forename: A N
authors.initials: AN
authors.lastname: Corps
authors.forename: L
authors.initials: L
authors.lastname: Cocco
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D004261:DNA Replication / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008934:Mitogens; D010712:Phosphatidic Acids / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D008934:Mitogens; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D007334:Insulin-Like Growth Factor I; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D001839:Bombesin