Dynamics of allosteric regulation of the phospholipase C-γ isozymes upon recruitment to membranes
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Abstract
Numerous receptor tyrosine kinases and immune receptors activate phospholipase C-γ (PLC-γ) isozymes at membranes to control diverse cellular processes including phagocytosis, migration, proliferation, and differentiation. The molecular details of this process are not well understood. Using hydrogen-deuterium exchange mass spectrometry, we show that PLC-γ1 is relatively inert to lipid vesicles that contain its substrate, phosphatidylinositol 4,5-bisphosphate (PIP 2 ), unless first bound to the kinase domain of the fibroblast growth factor receptor (FGFR1). Exchange occurs throughout PLC-γ1 and is exaggerated in PLC-γ1 containing an oncogenic substitution (D1165H) that allosterically activates the lipase. These data support a model whereby initial complex formation shifts the conformational equilibrium of PLC-γ1 to favor activation. This receptor-induced priming of PLC-γ1 also explains the capacity of a kinase-inactive fragment of FGFR1 to modestly enhance the lipase activity of PLC-γ1 operating on lipid vesicles but not a soluble analog of PIP 2 and highlights potential cooperativity between receptor engagement and membrane proximity. Priming is expected to be greatly enhanced for receptors embedded in membranes and nearly universal for the myriad of receptors and co-receptors that bind the PLC-γ isozymes.
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In the brain, there exists a remarkably tight window whereby a modest increase in PLCG2 enzymatic activity is associated with protective effects while reduced or robust increases in activity prove detrimental.
“Interestingly, in the brain, there exists a remarkably tight window whereby a modest increase in enzymatic activity is associated with protective effects while reduced or robust increases in activity prove detrimental.”
From PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology (2025) · cites this paper as [14]
The Introduction (page not provided) reports that a putative gain-of-function PLC-γ2 variant is associated with lower Alzheimer’s disease risk and may slow cognitive decline. It does not establish that the activity increase is modest, define a tight protective window, or say that reduced or robustly increased activity is detrimental in the brain. (LLM, conf=0.85)
Experimental — accuracy not yet measuredUpon tyrosine phosphorylation by upstream receptor complexes, PLCG2 undergoes an activating conformational change and is recruited to the plasma membrane.
“Upon tyrosine phosphorylation by upstream receptor complexes, PLCG2 undergoes an activating conformational change and is recruited to the plasma membrane.”
From PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology (2025) · cites this paper as [14]
The Introduction says PLC-γ2 requires Tyr759 phosphorylation for regulated activation, and the Discussion describes recruitment of PLC-γ isozymes to membrane-resident receptors as a step toward activation (pages not specified in our copy). But the paper's explicit sequence, described for PLC-γ1, places receptor-mediated recruitment before phosphorylation of the enzyme; it does not establish the claimed order for PLC-γ2. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAt the membrane, PLCG2 hydrolyzes PIP2 into IP3 and DAG.
“At the membrane, it hydrolyzes the lipid phosphatidylinositol (4,5)‐bisphosphate (PIP2) into the second messengers inositol (1,4,5)‐trisphosphate (IP3) and diacylglycerol (DAG).”
From PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology (2025) · cites this paper as [14]
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Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib
Woyach, J. A., Furman, R. R., Liu, T.-M., Ozer, H. G., Zapatka, M., Ruppert, A. S., Xue, L., Li, D. H.-H., Steggerda, S. M., Versele, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400029 · Cited by 1,275 · see citing works
ARUK Consortium, Sims, R., GERAD/PERADES, C., van der Lee, S. J., Naj, A. C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B. W., Boland, A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3916 · Cited by 1,126 · see citing works
Self-citationThe 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
Self-citationWatanabe, D., Hashimoto, S., Ishiai, M., Matsushita, M., Baba, Y., Kishimoto, T., Kurosaki, T., & Tsukada, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103675200 · Cited by 136 · see citing works
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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
Bunney, T. D., Esposito, D., Mas-Droux, C., Lamber, E., Baxendale, R. W., Martins, M., Cole, A., Svergun, D., Driscoll, P. C., & Katan, M. (2012) · Structure · doi:10.1016/j.str.2012.09.005 · Cited by 88 · 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
Walliser, C., Retlich, M., Harris, R., Everett, K. L., Josephs, M. B., Vatter, P., Esposito, D., Driscoll, P. C., Katan, M., Gierschik, P., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803316200 · Cited by 56 · see citing works
Liu, Y., Bunney, T. D., Khosa, S., Macé, K., Beckenbauer, K., Askwith, T., Maslen, S., Stubbs, C., de Oliveira, T. M., Sader, K., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2019.102607 · Cited by 42 · see citing works
Flagged first, then by citations
Research works printed but not linked: 42
- Arteaga CL Johnson MD Todderud G Coffey RJ Carpenter G Page DL 1991 Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas PNAS 88 10435 10439 10.1073/pnas.88.23.10435 1683701 PMC52943 · DOI
- Asokan SB Johnson HE Rahman A King SJ Rotty JD Lebedeva IP Haugh JM Bear JE 2014 Mesenchymal chemotaxis requires selective inactivation of myosin II at the leading edge via a noncanonical PLCγ/PKCα pathway Developmental Cell 31 747 760 10.1016/j.devcel.2014.10.024 25482883 PMC4276478 · DOI
- Bae JH Lew ED Yuzawa S Tomé F Lax I Schlessinger J 2009 The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site Cell 138 514 524 10.1016/j.cell.2009.05.028 19665973 PMC4764080 · DOI · Paper page
- Bunney TD Opaleye O Roe SM Vatter P Baxendale RW Walliser C Everett KL Josephs MB Christow C Rodrigues-Lima F Gierschik P Pearl LH Katan M 2009 Structural insights into formation of an active signaling complex between Rac and phospholipase C gamma 2 Molecular Cell 34 223 233 10.1016/j.molcel.2009.02.023 19394299 · DOI · Paper page
- Burgess WH Dionne CA Kaplow J Mudd R Friesel R Zilberstein A Schlessinger J Jaye M 1990 Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase Molecular and Cellular Biology 10 4770 4777 10.1128/mcb.10.9.4770-4777.1990 2167438 PMC361079 · DOI
- Chattopadhyay A Vecchi M Ji Q s Mernaugh R Carpenter G 1999 The role of individual SH2 domains in mediating association of phospholipase C-gamma1 with the activated EGF receptor The Journal of Biological Chemistry 274 26091 26097 10.1074/jbc.274.37.26091 10473558 · DOI
- DeBell KE Stoica BA Verí MC Di Baldassarre A Miscia S Graham LJ Rellahan BL Ishiai M Kurosaki T Bonvini E 1999 Functional independence and interdependence of the Src homology domains of phospholipase C-gamma1 in B-cell receptor signal transduction Molecular and Cellular Biology 19 7388 7398 10.1128/MCB.19.11.7388 10523627 PMC84732 · DOI
- DeBell K Graham L Reischl I Serrano C Bonvini E Rellahan B 2007 Intramolecular regulation of phospholipase C-gamma1 by its C-terminal Src homology 2 domain Molecular and Cellular Biology 27 854 863 10.1128/MCB.01400-06 17116690 PMC1800685 · DOI
- Dobbs JM Jenkins ML Burke JE 2020 Escherichia coli and Sf9 Contaminant Databases to Increase Efficiency of Tandem Mass Spectrometry Peptide Identification in Structural Mass Spectrometry Experiments Journal of the American Society for Mass Spectrometry 31 2202 2209 10.1021/jasms.0c00283 32869988 · DOI
- Ellis MV James SR Perisic O Downes CP Williams RL Katan M 1998 Catalytic domain of phosphoinositide-specific phospholipase C (PLC). Mutational analysis of residues within the active site and hydrophobic ridge of plcdelta1 The Journal of Biological Chemistry 273 11650 11659 10.1074/jbc.273.19.11650 9565585 · DOI
- Eswarakumar VP Lax I Schlessinger J 2005 Cellular signaling by fibroblast growth factor receptors Cytokine & Growth Factor Reviews 16 139 149 10.1016/j.cytogfr.2005.01.001 15863030 · DOI
- Gresset A Hicks SN Harden TK Sondek J 2010 Mechanism of phosphorylation-induced activation of phospholipase C-gamma isozymes The Journal of Biological Chemistry 285 35836 35847 10.1074/jbc.M110.166512 20807769 PMC2975207 · DOI
- Hajicek N Charpentier TH Rush JR Harden TK Sondek J 2013 Autoinhibition and phosphorylation-induced activation of phospholipase C-γ isozymes Biochemistry 52 4810 4819 10.1021/bi400433b 23777354 PMC3844103 · DOI
- Hajicek N Keith NC Siraliev-Perez E Temple BR Huang W Zhang Q Harden TK Sondek J 2019 Structural basis for the activation of PLC-γ isozymes by phosphorylation and cancer-associated mutations eLife 8 e51700 10.7554/eLife.51700 31889510 PMC7004563 · DOI · Paper page
- Horstman DA Chattopadhyay A Carpenter G 1999 The influence of deletion mutations on phospholipase C-gamma 1 activity Archives of Biochemistry and Biophysics 361 149 155 10.1006/abbi.1998.0978 9882440 · DOI
- Huang W Hicks SN Sondek J Zhang Q 2011 A fluorogenic, small molecule reporter for mammalian phospholipase C isozymes ACS Chemical Biology 6 223 228 10.1021/cb100308n 21158426 PMC3312000 · DOI
- Huang W Wang X Endo-Streeter S Barrett M Waybright J Wohlfeld C Hajicek N Harden TK Sondek J Zhang Q 2018 A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes The Journal of Biological Chemistry 293 1728 1735 10.1074/jbc.RA117.000926 29263090 PMC5798302 · DOI
- Ji QS Chattopadhyay A Vecchi M Carpenter G 1999 Physiological requirement for both SH2 domains for phospholipase C-gamma1 function and interaction with platelet-derived growth factor receptors Molecular and Cellular Biology 19 4961 4970 10.1128/MCB.19.7.4961 10373546 PMC84312 · DOI
- Kadamur G Ross EM 2013 Mammalian phospholipase C Annual Review of Physiology 75 127 154 10.1146/annurev-physiol-030212-183750 23140367 · DOI · Paper page
- Kataoka K Nagata Y Kitanaka A Shiraishi Y Shimamura T Yasunaga J-I Totoki Y Chiba K Sato-Otsubo A Nagae G Ishii R Muto S Kotani S Watatani Y Takeda J Sanada M Tanaka H Suzuki H Sato Y Shiozawa Y Yoshizato T Yoshida K Makishima H Iwanaga M Ma G Nosaka K Hishizawa M Itonaga H Imaizumi Y Munakata W Ogasawara H Sato T Sasai K Muramoto K Penova M Kawaguchi T Nakamura H Hama N Shide K Kubuki Y Hidaka T Kameda T Nakamaki T Ishiyama K Miyawaki S Yoon S-S Tobinai K Miyazaki Y Takaori-Kondo A Matsuda F Takeuchi K Nureki O Aburatani H Watanabe T Shibata T Matsuoka M Miyano S Shimoda K Ogawa S 2015 Integrated molecular analysis of adult T cell leukemia/lymphoma Nature Genetics 47 1304 1315 10.1038/ng.3415 26437031 · DOI
- Kim JW Sim SS Kim UH Nishibe S Wahl MI Carpenter G Rhee SG 1990 Tyrosine residues in bovine phospholipase C-gamma phosphorylated by the epidermal growth factor receptor in vitro The Journal of Biological Chemistry 265 3940 3943 1689310
- Kim HK Kim JW Zilberstein A Margolis B Kim JG Schlessinger J Rhee SG 1991 PDGF stimulation of inositol phospholipid hydrolysis requires PLC-gamma 1 phosphorylation on tyrosine residues 783 and 1254 Cell 65 435 441 10.1016/0092-8674(91)90461-7 1708307 · DOI
- Kim MJ Chang JS Park SK Hwang JI Ryu SH Suh PG 2000 Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1 Biochemistry 39 8674 8682 10.1021/bi992558t 10913276 · DOI
- Kleineidam L Chouraki V Próchnicki T van der Lee SJ Madrid-Márquez L Wagner-Thelen H Karaca I Weinhold L Wolfsgruber S Boland A Martino Adami PV Lewczuk P Popp J Brosseron F Jansen IE Hulsman M Kornhuber J Peters O Berr C Heun R Frölich L Tzourio C Dartigues J-F Hüll M Espinosa A Hernández I de Rojas I Orellana A Valero S Stringa N van Schoor NM Huisman M Scheltens P Alzheimer’s Disease Neuroimaging Initiative (ADNI) Rüther E Deleuze J-F Wiltfang J Tarraga L Schmid M Scherer M Riedel-Heller S Heneka MT Amouyel P Jessen F Boada M Maier W Schneider A González-Pérez A van der Flier WM Wagner M Lambert J-C Holstege H Sáez ME Latz E Ruiz A Ramirez A 2020 PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment Acta Neuropathologica 139 1025 1044 10.1007/s00401-020-02138-6 32166339 PMC7244617 · DOI · Paper page
- Law CL Chandran KA Sidorenko SP Clark EA 1996 Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk Molecular and Cellular Biology 16 1305 1315 10.1128/MCB.16.4.1305 8657103 PMC231114 · DOI
- Manna A Zhao H Wada J Balagopalan L Tagad HD Appella E Schuck P Samelson LE 2018 Cooperative assembly of a four-molecule signaling complex formed upon T cell antigen receptor activation PNAS 115 E11914 E11923 10.1073/pnas.1817142115 30510001 PMC6304999 · DOI · Paper page
- Masson GR Burke JE Ahn NG Anand GS Borchers C Brier S Bou-Assaf GM Engen JR Englander SW Faber J Garlish R Griffin PR Gross ML Guttman M Hamuro Y Heck AJR Houde D Iacob RE Jørgensen TJD Kaltashov IA Klinman JP Konermann L Man P Mayne L Pascal BD Reichmann D Skehel M Snijder J Strutzenberg TS Underbakke ES Wagner C Wales TE Walters BT Weis DD Wilson DJ Wintrode PL Zhang Z Zheng J Schriemer DC Rand KD 2019 Recommendations for performing, interpreting and reporting hydrogen deuterium exchange mass spectrometry (HDX-MS) experiments Nature Methods 16 595 602 10.1038/s41592-019-0459-y 31249422 PMC6614034 · DOI
- Mohammadi M Honegger AM Rotin D Fischer R Bellot F Li W Dionne CA Jaye M Rubinstein M Schlessinger J 1991 A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is A binding site for the SH2 domain of phospholipase C-gamma 1 Molecular and Cellular Biology 11 5068 5078 10.1128/mcb.11.10.5068-5078.1991 1656221 PMC361508 · DOI
- Nakanishi O Shibasaki F Hidaka M Homma Y Takenawa T 1993 Phospholipase C-gamma 1 associates with viral and cellular src kinases The Journal of Biological Chemistry 268 10754 10759 10.1016/S0021-9258(18)82049-X 8388373 · DOI
- Nishibe S Wahl MI Hernández-Sotomayor SM Tonks NK Rhee SG Carpenter G 1990 Increase of the catalytic activity of phospholipase C-gamma 1 by tyrosine phosphorylation Science (New York, N.Y.) 250 1253 1256 10.1126/science.1700866 1700866 · DOI
- Noh DY Shin SH Rhee SG 1995 Phosphoinositide-specific phospholipase C and mitogenic signaling Biochimica et Biophysica Acta 1242 99 113 10.1016/0304-419x(95)00006-0 7492569 · DOI
- Patel VM Flanagan CE Martins M Jones CL Butler RM Woollard WJ Bakr FS Yoxall A Begum N Katan M Whittaker SJ Mitchell TJ 2020 Frequent and Persistent PLCG1 Mutations in Sézary Cells Directly Enhance PLCγ1 Activity and Stimulate NFκB, AP-1, and NFAT Signaling The Journal of Investigative Dermatology 140 380 389 10.1016/j.jid.2019.07.693 31376383 · DOI
- Perez-Riverol Y Csordas A Bai J Bernal-Llinares M Hewapathirana S Kundu DJ Inuganti A Griss J Mayer G Eisenacher M Pérez E Uszkoreit J Pfeuffer J Sachsenberg T Yilmaz S Tiwary S Cox J Audain E Walzer M Jarnuczak AF Ternent T Brazma A Vizcaíno JA 2019 The PRIDE database and related tools and resources in 2019: improving support for quantification data Nucleic Acids Research 47 D442 D450 10.1093/nar/gky1106 30395289 PMC6323896 · DOI
- Poulin B Sekiya F Rhee SG 2000 Differential roles of the Src homology 2 domains of phospholipase C-gamma1 (PLC-gamma1) in platelet-derived growth factor-induced activation of PLC-gamma1 in intact cells The Journal of Biological Chemistry 275 6411 6416 10.1074/jbc.275.9.6411 10692443 · DOI
- Poulin B Sekiya F Rhee SG 2005 Intramolecular interaction between phosphorylated tyrosine-783 and the C-terminal Src homology 2 domain activates phospholipase C-gamma1 PNAS 102 4276 4281 10.1073/pnas.0409590102 15764700 PMC555506 · DOI
- Rouquette-Jazdanian AK Sommers CL Kortum RL Morrison DK Samelson LE 2012 LAT-independent Erk activation via Bam32-PLC-γ1-Pak1 complexes: GTPase-independent Pak1 activation Molecular Cell 48 298 312 10.1016/j.molcel.2012.08.011 22981863 PMC3483363 · DOI
- Schade A Walliser C Wist M Haas J Vatter P Kraus JM Filingeri D Havenith G Kestler HA Milner JD Gierschik P 2016 Cool-temperature-mediated activation of phospholipase C-γ2 in the human hereditary disease PLAID Cellular Signalling 28 1237 1251 10.1016/j.cellsig.2016.05.010 27196803 · DOI
- Schaeffer EM Debnath J Yap G McVicar D Liao XC Littman DR Sher A Varmus HE Lenardo MJ Schwartzberg PL 1999 Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity Science (New York, N.Y.) 284 638 641 10.1126/science.284.5414.638 10213685 · DOI
- Stariha JTB Hoffmann RM Hamelin DJ Burke JE 2021 Probing Protein-Membrane Interactions and Dynamics Using Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS Methods in Molecular Biology (Clifton, N.J.) 2263 465 485 10.1007/978-1-0716-1197-5_22 33877613 · DOI
- Tvorogov D Carpenter G 2002 EGF-dependent association of phospholipase C-gamma1 with C-Cbl Experimental Cell Research 277 86 94 10.1006/excr.2002.5545 12061819 · DOI
- Vetter ML Martin-Zanca D Parada LF Bishop JM Kaplan DR 1991 Nerve growth factor rapidly stimulates tyrosine phosphorylation of phospholipase C-gamma 1 by a kinase activity associated with the product of the trk protooncogene PNAS 88 5650 5654 10.1073/pnas.88.13.5650 1712104 PMC51935 · DOI
- Yablonski D Kadlecek T Weiss A 2001 Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT Molecular and Cellular Biology 21 4208 4218 10.1128/MCB.21.13.4208-4218.2001 11390650 PMC87082 · DOI
Cited by
Sorted by citations
PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology
Messenger, E. J., Baar, S. A., Bedford, L. M., Tsai, A. P., Lin, P. B., Ferguson, C. A., Xu, G., Wallace, A., Landreth, G. E., Lamb, B. T., et al. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70231 · Cited by 16 · see citing works
Shin, Y.-C., Plummer-Medeiros, A. M., Mungenast, A., Choi, H.-W., TenDyke, K., Zhu, X., Shepard, J., Sanders, K., Zhuang, N., Hu, L., et al. (2024) · Science Advances · doi:10.1126/sciadv.adn6037 · Cited by 7 · see citing works
- Authors
- Siraliev-Perez, E., Stariha, J. T., Hoffmann, R. M., Temple, B. R., Zhang, Q., Hajicek, N., Jenkins, M. L., Burke, J. E., & Sondek, J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Victoria (CA)
- University of British Columbia (CA)
- Corresponding author
- Burke, John E
- Sondek, John
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2022-06-16
- Volume
- 11
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC9203054
- OpenAlex
- W4282940735
- Cited by
- 18
- References
- 9
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 2 · 2023: 2 · 2022: 1
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNC Libraries
- Funders
- National Institutes of Health (R01-GM057391, R01-GM098894)
- Government of Canada (Natural Science and Engineering Research Council of Canada NSERC-2020-04241)
- Michael Smith Foundation for Health Research (Scholar Award 17686)
- National Science Foundation (DGE-1650116)
- 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 › Lipid Membrane Structure and Behavior
- Keywords
- phospholipase C-gamma1, allosteric regulation, membrane recruitment, phosphatidylinositol 4,5-bisphosphate, FGFR1, receptor tyrosine kinase signaling, hydrogen-deuterium exchange, lipid vesicles, conformational equilibrium, receptor co-receptor
- MeSH terms
- Allosteric Regulation, Enzyme Activation, Isoenzymes, Lipase, Lipids, Type C Phospholipases, Phosphorylation, Phospholipase C gamma
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