Involvement of nuclear PLCbeta1 in lamin B1 phosphorylation and G2/M cell cycle progression.
Inositide-specific phospholipase Cbeta1 (PLCbeta1) signaling in cell proliferation has been investigated thoroughly in the G(1) cell cycle phase. However, little is known about its involvement in G(2)/M progression. We used murine erythroleukemia cells to investigate the role of PLCbeta1 in G(2)/M cell cycle progression and screened a number of candidate intermediate players, particularly mitogen-activated protein kinase (MAPK) and protein kinase C (PKC), which can, potentially, transduce serum mitogenic stimulus and induce lamin B1 phosphorylation, leading to G(2)/M progression. We report that PLCbeta1 colocalizes and physically interacts with lamin B1. Studies of the effects of inhibitors and selective si-RNA mediated silencing showed a role of JNK, PKCalpha, PKCbetaI, and the beta1 isoform of PI-PLC in cell accumulation in G(2)/M [as observed by fluorescence-activated cell sorter (FACS)]. To shed light on the mechanism, we considered that the final signaling target was lamin B1 phosphorylation. When JNK, PKCalpha, or PLCbeta1 were silenced, lamin B1 exhibited a lower extent of phosphorylation, as compared to control. The salient features to emerge from these studies are a common pathway in which JNK is likely to represent a link between mitogenic stimulus and activation of PLCbeta1, and, foremost, the finding that the PLCbeta1-mediated pathway represents a functional nuclear inositide signaling in the G(2)/M transition.
Fiume
Roberta
R
Cellular Signaling Laboratory, Department of Human Anatomical Sciences, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
Ramazzotti
Giulia
G
Teti
Gabriella
G
Chiarini
Francesca
F
Faenza
Irene
I
Mazzotti
Giovanni
G
Billi
Anna Maria
AM
Cocco
Lucio
L
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D004789:Enzyme Activation; D016195:G2 Phase / Q000502:physiology*; D034921:Lamin Type B / Q000378:metabolism*; D051379:Mice; D054799:Phospholipase C beta / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism
D034921:Lamin Type B; D011493:Protein Kinase C; D054799:Phospholipase C beta