Nuclear inositol lipids. Relationship between growth factor induced metabolic changes and protein kinase C activity.
We have sought to establish the effect of mitogen treatment on nuclear inositol lipids and the relationship between inositol cycle products and hyperphosphorylation of nuclear proteins via PKC during the lag phase leading to the onset of DNA synthesis. Swiss 3T3 cells were labelled for 36 hr with high levels of [3H]-myo-inositol and the radioactivity in nuclear inositol phospholipids was measured. Treatment of cells for 2 min, but not for 4 hr, with mitogenic concentrations of insulin-like growth factor I and bombesin caused a marked decrease in PtdInsP and PtdInsP2. Moreover, in vivo phosphorylation of some nuclear proteins occurs later on. Among these proteins, histone H1 and 0.75 M PCA soluble polypeptide, with an apparent Mr of 21,000 as revealed by electrophoretic analysis, are phosphorylated in vitro by protein kinase C in isolated nuclei purified from 3T3 cells treated for 90 min with IGF-I and bombesin. Since these phosphorylative events follow the earlier changes in nuclear polyphoinositide metabolism induced by the same mitogen combination, it seems possible that these two phenomena are related to each other and trigger the synthetic machinery responsible for replicating DNA.
Cocco
L
L
Institutes of Human Anatomy, Universities of Chieti, Bologna, Italy.
Capitani
S
S
Martelli
A M
AM
Irvine
R F
RF
Gilmour
R S
RS
Maraldi
N M
NM
Barnabei
O
O
Manzoli
F A
FA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D013002:Somatomedins / Q000494:pharmacology*
D007295:Inositol Phosphates; D009687:Nuclear Proteins; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D013002:Somatomedins; D007294:Inositol; D007334:Insulin-Like Growth Factor I; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D001839:Bombesin