Calcium free inositol (1,4,5)-trisphosphate stimulates protein kinase C dependent protein phosphorylation in nuclei isolated from mitogen-treated Swiss 3T3 cells.
As a step towards the elucidation of the role played by nuclear polyphosphoinositides, we have investigated the effect of exogenous calcium free inositol (1,4,5)-trisphosphate on the in vitro phosphorylation of proteins in nuclei prepared from Swiss 3T3 cells treated with bombesin and insulin-like growth factor I. When present in combination with phosphatidylserine, inositol (1,4,5)-trisphosphate enhanced the phosphorylation of two nuclear proteins, Mr 21,000 and 31,000, as well as of exogenous histone H1, to the same extent as a combination of phosphatidylserine and diacylglycerol. Inositol (1,4,5)-trisphosphate alone had no effect. This stimulation could be abolished by the protein kinase C inhibitor sphingosine and by EGTA, while could be restored by a combination of phosphatidylserine and exogenous Ca+(+) ions. These results raise the possibility that inositol (1,4,5)-trisphosphate is capable of liberating Ca+(+) ions from a nuclear store thus stimulating protein kinase C activity.
Martelli
A M
AM
Istituto di Anatomia Umana Normale, Bologna, Italy.
Gilmour
R S
RS
Manzoli
F A
FA
Cocco
L
L
D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
D006657:Histones; D009687:Nuclear Proteins; D004533:Egtazic Acid; D007334:Insulin-Like Growth Factor I; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D001839:Bombesin; D002118:Calcium