Involvement of nuclear PLCbeta1 in lamin B1 phosphorylation and G2/M cell cycle progression.

Abstract

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.

• Authors: Roberta Fiume, Giulia Ramazzotti, Gabriella Teti, Francesca Chiarini, Irene Faenza, Giovanni Mazzotti, Anna Maria Billi, Lucio Cocco
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 23 Issue 3 Pg. 957-66 (Mar 2009) ISSN: 1530-6860 [Electronic] United States
• PMID: 19028838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lamin Type B
• lamin B1
• Protein Kinase C
• Phospholipase C beta

Topics

• Animals
• Cell Division (physiology)
• Cell Line
• Cell Proliferation
• Enzyme Activation
• G2 Phase (physiology)
• Lamin Type B (metabolism)
• Mice
• Phospholipase C beta (metabolism)
• Phosphorylation
• Protein Kinase C (metabolism)