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Physiol. Rev. 80: 1291-1335, 2000;
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Physiological Reviews, Vol. 80, No. 4, October 2000, pp. 1291-1335
Copyright ©2000 by the American Physiological Society

Structure, Function, and Control of Phosphoinositide-Specific Phospholipase C

Mario J. Rebecchi and Srinivas N. Pentyala

Departments of Anesthesiology and Physiology and Biophysics, School of Medicine, State University of New York, Stony Brook, New York

Rebecchi, Mario J. and Srinivas N. Pentyala. Structure, Function, and Control of Phosphoinositide-Specific Phospholipase C. Physiol. Rev. 80: 1291-1335, 2000.Phosphoinositide-specific phospholipase C (PLC) subtypes beta , gamma , and delta  comprise a related group of multidomain phosphodiesterases that cleave the polar head groups from inositol lipids. Activated by all classes of cell surface receptor, these enzymes generate the ubiquitous second messengers inositol 1,4,5-trisphosphate and diacylglycerol. The last 5 years have seen remarkable advances in our understanding of the molecular and biological facets of PLCs. New insights into their multidomain arrangement and catalytic mechanism have been gained from crystallographic studies of PLC-delta 1 , while new modes of controlling PLC activity have been uncovered in cellular studies. Most notable is the realization that PLC-beta , -gamma , and -delta isoforms act in concert, each contributing to a specific aspect of the cellular response. Clues to their true biological roles were also obtained. Long assumed to function broadly in calcium-regulated processes, genetic studies in yeast, slime molds, plants, flies, and mammals point to specific and conditional roles for each PLC isoform in cell signaling and development. In this review we consider each subtype of PLC in organisms ranging from yeast to mammals and discuss their molecular regulation and biological function.




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M. K. Wilkerson, T. J. Heppner, A. D. Bonev, and M. T. Nelson
Inositol trisphosphate receptor calcium release is required for cerebral artery smooth muscle cell proliferation
Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H240 - H247.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
Y. Nakamura, Y. Hamada, T. Fujiwara, H. Enomoto, T. Hiroe, S. Tanaka, M. Nose, M. Nakahara, N. Yoshida, T. Takenawa, et al.
Phospholipase C-{delta}1 and -{delta}3 Are Essential in the Trophoblast for Placental Development
Mol. Cell. Biol., December 15, 2005; 25(24): 10979 - 10988.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
T. Piechulek, T. Rehlen, C. Walliser, P. Vatter, B. Moepps, and P. Gierschik
Isozyme-specific Stimulation of Phospholipase C-{gamma}2 by Rac GTPases
J. Biol. Chem., November 25, 2005; 280(47): 38923 - 38931.
[Abstract] [Full Text] [PDF]


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J EndocrinolHome page
E Houdeau, A Levy, and S Mhaouty-Kodja
Up-regulation of rat myometrial phospholipases C{beta}1 and C{beta}3 correlates with increased term sensitivity to carbachol and oxytocin
J. Endocrinol., November 1, 2005; 187(2): 197 - 204.
[Abstract] [Full Text] [PDF]


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J AndrolHome page
H. Harayama, T. Murase, and M. Miyake
A Cyclic Adenosine 3',5'-Monophosphate Stimulates Phospholipase C{gamma}1-Calcium Signaling via the Activation of Tyrosine Kinase in Boar Spermatozoa
J Androl, November 1, 2005; 26(6): 732 - 740.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
H. Frecker, S. Munk, H. Wang, and C. Whiteside
Mesangial cell-reduced Ca2+ signaling in high glucose is due to inactivation of phospholipase C-{beta}3 by protein kinase C
Am J Physiol Renal Physiol, November 1, 2005; 289(5): F1078 - F1087.
[Abstract] [Full Text] [PDF]


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J BiochemHome page
Y. Irino, M. Ichinohe, Y. Nakamura, M. Nakahara, and K. Fukami
Phospholipase C{delta}4 Associates with Glutamate Receptor Interacting Protein 1 in Testis
J. Biochem., October 1, 2005; 138(4): 451 - 456.
[Abstract] [Full Text] [PDF]


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ScienceHome page
M. Rao and S. Sockanathan
Transmembrane Protein GDE2 Induces Motor Neuron Differentiation in Vivo
Science, September 30, 2005; 309(5744): 2212 - 2215.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. Nakahara, M. Shimozawa, Y. Nakamura, Y. Irino, M. Morita, Y. Kudo, and K. Fukami
A Novel Phospholipase C, PLC{eta}2, Is a Neuron-specific Isozyme
J. Biol. Chem., August 12, 2005; 280(32): 29128 - 29134.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
T. Maejima, S. Oka, Y. Hashimotodani, T. Ohno-Shosaku, A. Aiba, D. Wu, K. Waku, T. Sugiura, and M. Kano
Synaptically Driven Endocannabinoid Release Requires Ca2+-Assisted Metabotropic Glutamate Receptor Subtype 1 to Phospholipase C {beta}4 Signaling Cascade in the Cerebellum
J. Neurosci., July 20, 2005; 25(29): 6826 - 6835.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
P. J. Bartlett, K. W. Young, S. R. Nahorski, and R. A. J. Challiss
Single Cell Analysis and Temporal Profiling of Agonist-mediated Inositol 1,4,5-Trisphosphate, Ca2+, Diacylglycerol, and Protein Kinase C Signaling using Fluorescent Biosensors
J. Biol. Chem., June 10, 2005; 280(23): 21837 - 21846.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
R. S. Sidhu, R. R. Clough, and R. P. Bhullar
Regulation of Phospholipase C-{delta}1 through Direct Interactions with the Small GTPase Ral and Calmodulin
J. Biol. Chem., June 10, 2005; 280(23): 21933 - 21941.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
Z. Kouchi, T. Shikano, Y. Nakamura, H. Shirakawa, K. Fukami, and S. Miyazaki
The Role of EF-hand Domains and C2 Domain in Regulation of Enzymatic Activity of Phospholipase C{zeta}
J. Biol. Chem., June 3, 2005; 280(22): 21015 - 21021.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
C. J. Serrano, L. Graham, K. DeBell, R. Rawat, M. C. Veri, E. Bonvini, B. L. Rellahan, and I. G. Reischl
A New Tyrosine Phosphorylation Site in PLC{gamma}1: The Role of Tyrosine 775 in Immune Receptor Signaling
J. Immunol., May 15, 2005; 174(10): 6233 - 6237.
[Abstract] [Full Text] [PDF]


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Eur Respir JHome page
R. Goggel and S. Uhlig
The inositol trisphosphate pathway mediates platelet-activating-factor-induced pulmonary oedema
Eur. Respir. J., May 1, 2005; 25(5): 849 - 857.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
C. Hisatsune, K. Nakamura, Y. Kuroda, T. Nakamura, and K. Mikoshiba
Amplification of Ca2+ Signaling by Diacylglycerol-mediated Inositol 1,4,5-Trisphosphate Production
J. Biol. Chem., March 25, 2005; 280(12): 11723 - 11730.
[Abstract] [Full Text] [PDF]


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JEMHome page
J. Sasaki, T. Sasaki, M. Yamazaki, K. Matsuoka, C. Taya, H. Shitara, S. Takasuga, M. Nishio, K. Mizuno, T. Wada, et al.
Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I {alpha}
J. Exp. Med., March 21, 2005; 201(6): 859 - 870.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. Iwai, Y. Tateishi, M. Hattori, A. Mizutani, T. Nakamura, A. Futatsugi, T. Inoue, T. Furuichi, T. Michikawa, and K. Mikoshiba
Molecular Cloning of Mouse Type 2 and Type 3 Inositol 1,4,5-Trisphosphate Receptors and Identification of a Novel Type 2 Receptor Splice Variant
J. Biol. Chem., March 18, 2005; 280(11): 10305 - 10317.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
Y. Guo, M. Rebecchi, and S. Scarlata
Phospholipase C{beta}2 Binds to and Inhibits Phospholipase C{delta}1
J. Biol. Chem., January 14, 2005; 280(2): 1438 - 1447.
[Abstract] [Full Text] [PDF]


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Pharmacol. Rev.Home page
R. Laporte, A. Hui, and I. Laher
Pharmacological Modulation of Sarcoplasmic Reticulum Function in Smooth Muscle
Pharmacol. Rev., December 1, 2004; 56(4): 439 - 513.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
K. S. Murthy, H. Zhou, J. Huang, and S. N. Pentyala
Activation of PLC-{delta}1 by Gi/o-coupled receptor agonists
Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1679 - C1687.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
G. Asemu, N. S. Dhalla, and P. S. Tappia
Inhibition of PLC improves postischemic recovery in isolated rat heart
Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2598 - H2605.
[Abstract] [Full Text] [PDF]


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IOVSHome page
S. Landreville, S. Coulombe, P. Carrier, M. H. Gelb, S. L. Guerin, and C. Salesse
Expression of Phospholipases A2 and C in Human Corneal Epithelial Cells
Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 3997 - 4003.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
Y. Okubo, S. Kakizawa, K. Hirose, and M. Iino
Cross Talk between Metabotropic and Ionotropic Glutamate Receptor-Mediated Signaling in Parallel Fiber-Induced Inositol 1,4,5-Trisphosphate Production in Cerebellar Purkinje Cells
J. Neurosci., October 27, 2004; 24(43): 9513 - 9520.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
Y. Uezono, M. Kaibara, O. Murasaki, and K. Taniyama
Involvement of G protein {beta}{gamma}-subunits in diverse signaling induced by Gi/o-coupled receptors: study using the Xenopus oocyte expression system
Am J Physiol Cell Physiol, October 1, 2004; 287(4): C885 - C894.
[Abstract] [Full Text] [PDF]


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Mol Biol EvolHome page
T. Nagata, S. Iizumi, K. Satoh, H. Ooka, J. Kawai, P. Carninci, Y. Hayashizaki, Y. Otomo, K. Murakami, K. Matsubara, et al.
Comparative Analysis of Plant and Animal Calcium Signal Transduction Element Using Plant Full-Length cDNA Data
Mol. Biol. Evol., October 1, 2004; 21(10): 1855 - 1870.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
G. Chen, P. Raman, P. Bhonagiri, A. B. Strawbridge, G. R. Pattar, and J. S. Elmendorf
Protective Effect of Phosphatidylinositol 4,5-Bisphosphate against Cortical Filamentous Actin Loss and Insulin Resistance Induced by Sustained Exposure of 3T3-L1 Adipocytes to Insulin
J. Biol. Chem., September 17, 2004; 279(38): 39705 - 39709.
[Abstract] [Full Text] [PDF]


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JCBHome page
G. Mouneimne, L. Soon, V. DesMarais, M. Sidani, X. Song, S.-C. Yip, M. Ghosh, R. Eddy, J. M. Backer, and J. Condeelis
Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation
J. Cell Biol., August 30, 2004; 166(5): 697 - 708.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
M. Isshiki, A. Mutoh, and T. Fujita
Subcortical Ca2+ Waves Sneaking Under the Plasma Membrane in Endothelial Cells
Circ. Res., August 6, 2004; 95(3): e11 - e21.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. Hirose, J. Kitano, Y. Nakajima, K. Moriyoshi, S. Yanagi, H. Yamamura, T. Muto, H. Jingami, and S. Nakanishi
Phosphorylation and Recruitment of Syk by Immunoreceptor Tyrosine-based Activation Motif-based Phosphorylation of Tamalin
J. Biol. Chem., July 30, 2004; 279(31): 32308 - 32315.
[Abstract] [Full Text] [PDF]


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Hum Reprod UpdateHome page
N. P.Y. Lee and C. Y. Cheng
Ectoplasmic specialization, a testis-specific cell-cell actin-based adherens junction type: is this a potential target for male contraceptive development?
Hum. Reprod. Update, July 1, 2004; 10(4): 349 - 369.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
J. L. Leaney, A. Benians, S. Brown, M. Nobles, D. Kelly, and A. Tinker
Rapid desensitization of G protein-gated inwardly rectifying K+ currents is determined by G protein cycle
Am J Physiol Cell Physiol, July 1, 2004; 287(1): C182 - C191.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. Martin, R. Goggel, A.-R. Ressmeyer, and S. Uhlig
Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase
Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L250 - L257.
[Abstract] [Full Text] [PDF]




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