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G-protein-activated phospholipase C-β, new partners for cell polarity proteins Par3 and Par6

Oncogene volume 24, pages 4293–4300 (2005)Cite this article

Abstract

Cell polarity and asymmetric cell division are fundamental traits of all living cells and play an essential role in embryonic development, neuronal cell chirality formation, and maintenance of mammalian epithelial cell morphology. Heterotrimeric GTP-binding proteins (G proteins) are involved in directing cell polarity and asymmetric cell division in different organisms. However, the mechanism for G-protein-mediated cell polarity and asymmetric cell division is poorly understood. In this study, we have demonstrated that G-protein-activated phospholipase C-β (PLC-β) interacts with cell polarity proteins Par3 and Par6 (Par: partition-defective) to form protein complexes and to mediate downstream signal transduction. The interactions between PLC-β and Par proteins are direct and require the extreme C-terminal-specific sequence motifs of PLC-β and the PDZ (PSD95/Dlg/ZO-1) domains of Par proteins. Binding of Par proteins with PLC-β stimulates PLC-β enzymatic activity, leading to the hydrolysis of phosphatidylinositol-4,5-bisphosphate, and the production of diacylglycerol and inositol 1,4,5-triphosphate, important mediators in cell polarity and cell asymmetric division processes. Furthermore, we have shown that coexpression of PLC-β with Par proteins induces transcriptional activation coupled to intracellular Ca2+ and the Wnt signaling pathway. Therefore, our data suggest that the interaction of PLC-β with cell polarity Par proteins may serve as a nexus to transduce extracellular signals to transcriptional regulation through G-protein-mediated signaling pathway in cell polarity and cell asymmetric division.

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Abbreviations

Par:

partition-defective

GPCR:

G-protein-coupled receptor

PIP2:

phosphatidylinositol-4,5-biphosphate

IP3:

inositol 1,4,5 triphosphate

DAG:

diacylglycerol

PDZ domain:

PSD95/Dlg/ZO-1

PLC:

phospholipase C

IP:

immunoprecipitation

WB:

Western blot

SRE:

serum response element

NF-AT:

nuclear factor of activated T cells

Lef:

lymphoid enhancer factor

TCF4:

T-cell factor 4

PKC:

protein kinase C

G protein:

heterotrimeric GTP-binding protein

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Acknowledgements

This work was supported by a grant from National Institute of Health (R01 HL64792) and a Scientist Development Award from American Heart Association National (0030160N) to M Liu. We thank Dr Ian G Macara (University of Virginia Health Sciences Center, Charlottesville, VA, USA) and Dr Tony Pawson at Samuel Lunenfeld Research Institute, Canada, for kindly providing the human myc-Par3 and myc-Par6 constructs.

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  1. Department of Medical Biochemistry and Genetics, Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 2121 W Holcombe Blvd, Houston, TX, 77030, USA

    Yi Cai, Lewis J Stafford, Brad A Bryan, Dianne Mitchell & Mingyao Liu

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Correspondence to Mingyao Liu.

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Cai, Y., Stafford, L., Bryan, B. et al. G-protein-activated phospholipase C-β, new partners for cell polarity proteins Par3 and Par6. Oncogene 24, 4293–4300 (2005). https://doi.org/10.1038/sj.onc.1208593

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