Inositides in the nucleus: taking stock of PLC beta 1.
The nucleus was shown to be a site for inositol lipid cycle which can be affected by treatment of quiescent cells with growth factors such as IGF-I. In fact, the exposure of Swiss 3T3 cells to IGF-I results in a rapid and transient increase in nuclear PLC beta 1 activity. In addition, several other reports have shown the involvement of PLC beta 1 in nuclear signalling in different cell types. Indeed, PLC beta 1 differs from the PLC gamma and della isozymes in that it has a long COOH-terminal sequence which contains a cluster of lysine residues that are critical for association with the nucleus. Although the demonstration of PtInsP and PtdInsP2 hydrolysis by nuclear PLC beta 1 established the existence of nuclear PLC signalling, the significance of this autonomous pathway in the nucleus has yet to be thoroughly clarified. By inducing both the inhibition of PLC beta 1 expression by antisense RNA and its overexpression we show that this nuclear PLC is essential for the onset of DNA synthesis following IGF-I stimulation of quiescent Swiss 3T3 cells. Moreover, using a different cell system, i.e. Friend erythroleukemia cells induced to differentiate towards erythrocytes, it has been evidenced that there is a relationship between the expression and activity of nuclear PLC beta 1 and the association of PI-PT alpha with the nucleus in that, when PLC activity ceases, in differentiated and resting cells at the same time there is a dramatic decrease of the association of PI-PT alpha with the nucleus.
Institute of Human Anatomy, University of Bologna, Italy.
L
L
Cocco
S
S
Capitani
N M
NM
Maraldi
G
G
Mazzotti
O
O
Barnabei
R
R
Rizzoli
R S
RS
Gilmour
K W
KW
Wirtz
S G
SG
Rhee
F A
FA
Manzoli
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology*; D015536:Down-Regulation / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism*; D054799:Phospholipase C beta; D049294:Phospholipid Transfer Proteins; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*
D002352:Carrier Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse; C518035:Plcb1 protein, rat