Regulation of Phosphoinositide-Specific Phospholipase C
Open accessAbstract
Eleven distinct isoforms of phosphoinositide-specific phospholipase C (PLC), which are grouped into four subfamilies (beta, gamma, delta, and epsilon), have been identified in mammals. These isozymes catalyze the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] to inositol 1,4,5-trisphosphate and diacylglycerol in response to the activation of more than 100 different cell surface receptors. All PLC isoforms contain X and Y domains, which form the catalytic core, as well as various combinations of regulatory domains that are common to many other signaling proteins. These regulatory domains serve to target PLC isozymes to the vicinity of their substrate or activators through protein-protein or protein-lipid interactions. These domains (with their binding partners in parentheses or brackets) include the pleckstrin homology (PH) domain [PtdIns(3)P, beta gamma subunits of G proteins] and the COOH-terminal region including the C2 domain (GTP-bound alpha subunit of Gq) of PLC-beta; the PH domain [PtdIns(3,4,5)P3] and Src homology 2 domain [tyrosine-phosphorylated proteins, PtdIns(3,4,5)P3] of PLC-gamma; the PH domain [PtdIns(4,5)P2] and C2 domain (Ca2+) of PLC-delta; and the Ras binding domain (GTP-bound Ras) of PLC-epsilon. The presence of distinct regulatory domains in PLC isoforms renders them susceptible to different modes of activation. Given that the partners that interact with these regulatory domains of PLC isozymes are generated or eliminated in specific…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PLCγ2 is a PIP2 metabolising enzyme recruited to the cell membrane upon activation by tyrosine kinase and modulates immune signals impacting cell fate and function.
“The protein product of PLCG2 (PLCγ2) is a PIP2 metabolising enzyme that is recruited to the cell membrane upon activation by tyrosine kinase and modulates immune signals impacting cell fate and function, both in the brain and periphery [12, 13].”
From Heterozygous expression of the Alzheimer’s disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses (2022) · cites this paper as [12]
Cites
Regulation of Phosphoinositide-specific Phospholipase C Isozymes
Rhee, S. G., & Bae, Y. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.24.15045 · Cited by 876 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
KRAS Mutation: From Undruggable to Druggable in Cancer
Huang, L., Guo, Z., Wang, F., & Fu, L. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00780-4 · Cited by 1,127 · see citing works
The oxytocin receptor: from intracellular signaling to behavior
Jurek, B., & Neumann, I. D. (2018) · Physiological Reviews · doi:10.1152/physrev.00031.2017 · Cited by 999 · see citing works
Kadamur, G., & Ross, E. M. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183750 · Cited by 529 · see citing works
Regulation, signaling, and physiological functions of G-Proteins
Syrovatkina, V., Alegre, K. O., Dey, R., & Huang, X.-Y. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.08.002 · Cited by 498 · see citing works
Phospholipase Cγ2 Is Essential in the Functions of B Cell and Several Fc Receptors
Wang, D., Feng, J., Wen, R., Marine, J.-C., Sangster, M. Y., Parganas, E., Hoffmeyer, A., Jackson, C. W., Cleveland, J. L., Murray, P. J., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00005-4 · Cited by 475 · see citing works
Ras Conformational Ensembles, Allostery, and Signaling
Lu, S., Jang, H., Muratcioglu, S., Gursoy, A., Keskin, O., Nussinov, R., & Zhang, J. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00542 · Cited by 355 · see citing works
Chen, Y., Okano, K., Maeda, T., Chauhan, V., Golczak, M., Maeda, A., & Palczewski, K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.315432 · Cited by 229 · see citing works
Kurosaki, T., & Tsukada, S. (2000) · Immunity · doi:10.1016/s1074-7613(00)80153-3 · Cited by 223 · see citing works
The Phospholipase C Isozymes and Their Regulation
Gresset, A., Sondek, J., & Harden, T. K. (2012) · Subcellular Biochemistry · doi:10.1007/978-94-007-3012-0_3 · Cited by 196 · see citing works
Weber, M., Treanor, B., Depoil, D., Shinohara, H., Harwood, N. E., Hikida, M., Kurosaki, T., & Batista, F. D. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072619 · Cited by 170 · see citing works
Receptor Activation of NADPH Oxidases
Petry, A., Weitnauer, M., & Görlach, A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.3026 · Cited by 162 · see citing works
Phospholipase C–mediated hydrolysis of PIP2 releases ERM proteins from lymphocyte membrane
Hao, J.-J., Liu, Y., Kruhlak, M., Debell, K. E., Rellahan, B. L., & Shaw, S. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200807047 · Cited by 137 · see citing works
Phospholipase Cγ1 is essential for T cell development, activation, and tolerance
Fu, G., Chen, Y., Yu, M., Podd, A., Schuman, J., He, Y., Di, L., Yassai, M., Haribhai, D., North, P. E., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20090880 · Cited by 133 · see citing works
DESGESCO (Dementia Genetics Spanish Consortium), E. (. D. E. D. B., van der Lee, S. J., biobank), E. (. D. E. D., IFGC (International FTD-Genomics Consortium), I. (. I. P. D. G. C., IPDGC (The International Parkinson Disease Genomics Consortium), Dementia), R.-F. (. A. M. F. I. F.-T., (NBB), N. B. B., The GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, Conway, O. J., Jansen, I., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02026-8 · Cited by 120 · see citing works
Mechanism of B-Cell Receptor-Induced Phosphorylation and Activation of Phospholipase C-γ2
Kim, Y. J., Sekiya, F., Poulin, B., Bae, Y. S., & Rhee, S. G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.22.9986-9999.2004 · Cited by 126 · see citing works
Self-citationPotential Contribution of Exosomes to the Prion-Like Propagation of Lesions in Alzheimer’s Disease
Vingtdeux, V., Sergeant, N., & Buée, L. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00229 · Cited by 116 · see citing works
Dysfunction of phospholipase Cγ in immune disorders and cancer
Koss, H., Bunney, T. D., Behjati, S., & Katan, M. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.09.004 · Cited by 115 · see citing works
Purinergic signalling and intercellular Ca2+ wave propagation in the organ of Corti
Piazza, V., Ciubotaru, C. D., Gale, J. E., & Mammano, F. (2007) · Cell Calcium · doi:10.1016/j.ceca.2006.05.005 · Cited by 105 · see citing works
GABA induces terminal differentiation of <i>Dictyostelium</i> through a GABAB receptor
Anjard, C., & Loomis, W. F. (2006) · Development · doi:10.1242/dev.02399 · Cited by 86 · see citing works
Isozyme-specific stimulation of phospholipase C-γ2 by Rac GTPases
Piechulek, T., Rehlen, T., Walliser, C., Vatter, P., Moepps, B., & Gierschik, P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509396200 · Cited by 80 · see citing works
Phospholipase Cβ Is Critical for T Cell Chemotaxis
Bach, T. L., Chen, Q.-M., Kerr, W. T., Wang, Y., Lian, L., Choi, J. K., Wu, D., Kazanietz, M. G., Koretzky, G. A., Zigmond, S., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.4.2223 · Cited by 68 · see citing works
Bolaños, C. A., Perrotti, L. I., Edwards, S., Eisch, A. J., Barrot, M., Olson, V. G., Russell, D. S., Neve, R. L., & Nestler, E. J. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-20-07569.2003 · Cited by 62 · see citing works
Liu, W., Cai, M.-J., Zheng, C.-C., Wang, J.-X., & Zhao, X.-F. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.547018 · Cited by 59 · see citing works
Capel, R. A., Bose, S. J., Collins, T. P., Rajasundaram, S., Ayagama, T., Zaccolo, M., Burton, R.-A. B., & Terrar, D. A. (2021) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00380.2020 · Cited by 40 · see citing works
Liu, W., Cai, M.-J., Wang, J.-X., & Zhao, X.-F. (2014) · Endocrinology · doi:10.1210/en.2013-2020 · Cited by 38 · see citing works
Manaboon, M., Iga, M., Iwami, M., & Sakurai, S. (2009) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2008.10.013 · Cited by 37 · see citing works
Nieto-Gonzalez, J. L., & Jensen, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067318 · Cited by 35 · see citing works
Essential Role of Phospholipase Cγ2 in Early B-Cell Development and Myc-Mediated Lymphomagenesis
Wen, R., Chen, Y., Bai, L., Fu, G., Schuman, J., Dai, X., Zeng, H., Yang, C., Stephan, R. P., Cleveland, J. L., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00839-06 · Cited by 34 · see citing works
Solomon, S., Sampathkumar, N. K., Carre, I., Mondal, M., Chennell, G., Vernon, A. C., Ruepp, M.-D., & Mitchell, J. C. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04473-1 · Cited by 23 · see citing works
The novel phospholipase C activator, m-3M3FBS, induces monocytic leukemia cell apoptosis
Lee, Y.-N., Lee, H.-Y., Kim, J.-S., Park, C., Choi, Y. H., Lee, T. G., Ryu, S. H., Kwak, J.-Y., & Bae, Y.-S. (2005) · Cancer Letters · doi:10.1016/j.canlet.2004.09.017 · Cited by 18 · see citing works
G-protein αq participates in the steroid hormone 20-hydroxyecdysone nongenomic signal transduction
Ren, J., Li, X.-R., Liu, P.-C., Cai, M.-J., Liu, W., Wang, J.-X., & Zhao, X.-F. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.08.006 · Cited by 15 · see citing works
- Authors
- Rhee, S. G.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Rhee, Sue Goo
- ORCID
- Rhee, Sue Goo
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2001-06
- Volume
- 70
- Issue
- 1
- Pages
- 281-312
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- PMC
- PMC4781088
- OpenAlex
- W1958742527
- Cited by
- 1,628
- References
- 1
- Citations by year
- 2026: 15 · 2025: 30 · 2024: 22 · 2023: 35 · 2022: 30 · 2021: 27 · 2020: 33 · 2019: 30 · 2018: 38 · 2017: 40 · 2016: 41 · 2015: 54 · 2014: 70 · 2013: 70 · 2012: 73
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- phosphatidylinositol-specific phospholipase C, PLC isoforms, phospholipase C beta, phospholipase C-gamma, phosphatidylinositol 4,5-bisphosphate, inositol 1,4,5-trisphosphate, diacylglycerol, pleckstrin homology domain, C2 domain, SH2 domain, Ras-binding domain, G protein beta gamma subunits, phosphatidylinositol 3,4,5-trisphosphate, protein-protein interaction, protein-lipid interactions, signal transduction
- MeSH terms
- Cell Nucleus, Enzyme Activation, Isoenzymes, Phosphatidylinositols, Type C Phospholipases, Protein-Tyrosine Kinases, Signal Transduction, GTP-Binding Proteins, Protein Subunits
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
