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

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 dire...

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Veröffentlicht in:Oncogene 2005-06, Vol.24 (26), p.4293-4300
Hauptverfasser: Cai, Yi, Stafford, Lewis J, Bryan, Brad A, Mitchell, Dianne, Liu, Mingyao
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container_issue 26
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container_title Oncogene
container_volume 24
creator Cai, Yi
Stafford, Lewis J
Bryan, Brad A
Mitchell, Dianne
Liu, Mingyao
description 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 Ca 2+ 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.
doi_str_mv 10.1038/sj.onc.1208593
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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. 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subjects Adaptor Proteins, Signal Transducing
Apoptosis
Biological and medical sciences
Calcium (intracellular)
Calcium signalling
Carrier Proteins - biosynthesis
Carrier Proteins - metabolism
Cell Biology
Cell Culture Techniques
Cell division
Cell Division - physiology
Cell physiology
Cell Polarity - genetics
Cell Polarity - physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Chirality
Cytology
Diglycerides
Embryogenesis
Enzymatic activity
Epithelial cells
Fundamental and applied biological sciences. Psychology
Gene regulation
GTP-binding protein
GTP-Binding Proteins - pharmacology
Human Genetics
Humans
Hydrolysis
Inositol 1,4,5-trisphosphate receptors
Internal Medicine
Intracellular signalling
Isoenzymes - biosynthesis
Isoenzymes - pharmacology
Kidney - cytology
Kinases
Medicine
Medicine & Public Health
Molecular and cellular biology
Oncology
original-paper
Phosphatidylinositol 4,5-diphosphate
Phospholipase C
Phospholipase C beta
Polarity
Postsynaptic density proteins
Proteins
Receptors, Thrombin - biosynthesis
Receptors, Thrombin - metabolism
Signal Transduction
Transcription activation
Transcription, Genetic
Transfection
Type C Phospholipases - biosynthesis
Type C Phospholipases - pharmacology
Wnt protein
Zonula occludens-1 protein
title G-protein-activated phospholipase C-β, new partners for cell polarity proteins Par3 and Par6
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