BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=curation_notes.txthttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075.pdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=manifest.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075_url.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075.odehttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075-octave.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075-matlab.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=curation_image.jpeghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=BIOMD0000000075.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000075?filename=metadata.rdfprimaryOK200Harish DharuriManually curatedordinary differential equation modelL3V1https://www.ebi.ac.uk/biomodels/BIOMD000000007512771127falseBioModelsSBMLModelsXu2003 Phosphoinositide turnover2003MODEL3095606944Chang Xu, James Watras, L M LoewChang Xu12771127,
We studied the bradykinin-induced changes in phosphoinositide composition of N1E-115 neuroblastoma cells using a combination of biochemistry, microscope imaging, and mathematical modeling. Phosphatidylinositol-4,5-bisphosphate (PIP2) decreased over the first 30 s, and then recovered over the following 2-3 min. However, the rate and amount of inositol-1,4,5-trisphosphate (InsP3) production were much greater than the rate or amount of PIP2 decline. A mathematical model of phosphoinositide turnover based on this data predicted that PIP2 synthesis is also stimulated by bradykinin, causing an early transient increase in its concentration. This was subsequently confirmed experimentally. Then, we used single-cell microscopy to further examine phosphoinositide turnover by following the translocation of the pleckstrin homology domain of PLCdelta1 fused to green fluorescent protein (PH-GFP). The observed time course could be simulated by incorporating binding of PIP2 and InsP3 to PH-GFP into the model that had been used to analyze the biochemistry. Furthermore, this analysis could help to resolve a controversy over whether the translocation of PH-GFP from membrane to cytosol is due to a decrease in PIP2 on the membrane or an increase in InsP3 in cytosol; by computationally clamping the concentrations of each of these compounds, the model shows how both contribute to the dynamics of probe translocation.. 4, 161.
Department of Physiology, University of Connecticut Health Center, Farmington, CT 06030, USA.hdharuri@cds.caltech.eduCalifornia Institute of TechnologyBIOMD0000000075We studied the bradykinin-induced changes in phosphoinositide composition of N1E-115 neuroblastoma cells using a combination of biochemistry, microscope imaging, and mathematical modeling. Phosphatidylinositol-4,5-bisphosphate (PIP2) decreased over the first 30 s, and then recovered over the following 2-3 min. However, the rate and amount of inositol-1,4,5-trisphosphate (InsP3) production were much greater than the rate or amount of PIP2 decline. A mathematical model of phosphoinositide turnover based on this data predicted that PIP2 synthesis is also stimulated by bradykinin, causing an early transient increase in its concentration. This was subsequently confirmed experimentally. Then, we used single-cell microscopy to further examine phosphoinositide turnover by following the translocation of the pleckstrin homology domain of PLCdelta1 fused to green fluorescent protein (PH-GFP). The observed time course could be simulated by incorporating binding of PIP2 and InsP3 to PH-GFP into the model that had been used to analyze the biochemistry. Furthermore, this analysis could help to resolve a controversy over whether the translocation of PH-GFP from membrane to cytosol is due to a decrease in PIP2 on the membrane or an increase in InsP3 in cytosol; by computationally clamping the concentrations of each of these compounds, the model shows how both contribute to the dynamics of probe translocation.Kinetic analysis of receptor-activated phosphoinositide turnover.Xu Chang C, Watras James J, Loew Leslie M LMPhosphoinositides, Inositol Phospholipids, Phosphoinositide, Inositol, Inositide, Inositol Phosphoglyceride, Inositol Phospholipid, Phospholipid, Inositol Phosphoglycerides, Phospholipids, Inositide Phospholipids, Inositol., Phosphatidylinositol, Phosphatidyl, Phosphoglyceride, Phosphoglycerides, Inositide Phospholipid, PtdIns, Phosphatidyl InositolMuch, GFP cell, Pleckstrin, sci, Bradykinin Diacetate, Homology Domain, Long Term, aa, dmTAF[[II]]230, Mesoinositol, 1, HOW, How, 2, 3, 4, Decreased, 5, Fs(3)Hor, Theory, Utility Theories, Theoretical Study, BK, TFIID TAF250, L-Arg-L-Pro-L-Pro-Gly-L-Phe-L-Ser-L-Pro-L-Phe-L-Arg, cel, Reduced, Nonmigrant, Tissue, L-myo-Inositol, Economic Policies, stru, Of Each, Living Costs, l(3)S053606, Hand-Held Microscopy, Arg Pro Pro Gly Phe Ser Pro Phe Arg, NTef2, Transient, Based, (1-D-Arg)-Isomer, AI047805, Inositol Phospholipids, PLASMA MEMBRANE INTRINSIC PROTEIN 2, decreased, Household Consumptions, Economic, fused to, INCREASED, NICR1047, dTAF[[II]]230, Followed By, (1r, Indices, Index, Patient recovered, TAF200, Longterm Effect, MT (more than), integral to membrane, Light, Course, predicted, Fs(3)Sz11, RESOLVE Multishot Diffusion Weighted Echoplanar Scanning, Economic Condition, Experimental, (5-D-Phe-8-D-Phe)-Isomer, Dm1, Utility Theory, Domains, Macroeconomic, TL., Confirmed, Pleckstrin Homology Domain, (2-D-Pro-7-D-Pro)-Isomer, Migrants and Transients, 1L-myo-Inositol, Mathematics, phosphatidylinositols, Consumer Price Indices, (7-D-Pro)-Isomer, Contributory, 5/4, Home, Theoretical Models, Hand Held Microscopy, Condition, Phosphoinositides, Taf250, RESOLVE Diffuse Weighted Imaging, GT, Kallidin I, 6-HEXAHYDROXY-CYCLOHEXANE, CG2684, Cytosols, Migrants, fused, Mathematical Model, TAF230, RPPGFSPFR, Induced, Williams-Fitzgerald-Flaujeac factor, Policies, Inositide, Experimental Models, Effects, Fitzgerald factor, Phosphatidylinositol, Utility, Ph-, protein-containing complex, Aid, CG7826, Theoretical, Inducible, Easterlin, CG7835, Gene Products, CG42273, Phosphatidyl, Assisted, dTAF[[II]]250, Longterm, cell, Tissues, ligand, Inducing, Microeconomic Factors, Bradykinin, 2-3, Long-Term, Theoretic, Worker, Solution, Study, dTAF250, Mathematical, Capital, Resolve, RESOLVE DWI, N1E-115, Bradykinin Hydrochloride, Philadelphia Chromosome Negative, PHASE II/III TRIAL, (8-D-Phe)-Isomer, SINGLE, (3-D-Pro-7-D-Pro)-Isomer, Protocol Treatment Course, Conditions, Proteins, 5-trans-4, Model (Theoretical), Phosphoglycerides, Factor, BG:DS00004.13, qkr, l(3)S090417, Cell, dTAF230, MT, native protein, Inositol Phosphoglycerides, Consumer Price Index, Consumer Price, Confirmatory, Simple Microscopy, Clamping, KH93F, Long Term Effects, chemical analysis, TAF[[II]]250/230, NB, Ana, Induce, PIP2, Ph Negative, AU020952, Taf[[II]]250, Single Person, Phospholipids, Compound Microscopy, Chiro-Inositol, (5-D-Phe)-Isomer, Myoinositol, Increased, OAF2, Lds, Longterm Effects, ME-IV, Gene Proteins, inositols, Models (Theoretical), Causation, Compound, Nomads, Solitary, Recovered from Adverse Event, PH, RESOLVE, PI, Alone, Recovered, Trial Phase 2-3, determination, Theoretical Model, Greater Than, Dambose, Combination, Imaging, protein, PtdIns, Bradykinin Acetate, Mathematical Models, Meat sugar, Membrane Tissues, Light Microscopy, i-inositol, Min, Kallidin II, protein aggregate, present in fewer numbers in organism, Microeconomic, Effect, l(3)j5D5, DmelCG42273, multicellular organismal biosynthetic process, 24B, D-myo-Inositol, inosite, single-organism biosynthetic process, DmelCG2684, Migrant Worker, Observed, Household Consumption, Simple, membrane region, min, Pleckstrin Homology, mAPC, Constrictions, CG10293, Phosphatidyl Inositol, (2-D-Pro)-Isomer, 2R, Homology Domains, l(3)j5B5, RESOLVE Multishot Diffusion Weighted Echoplanar Imaging, Subsequent, Hand-Held, High molecular weight kininogen, Squatters, Theories, TL, Long-Term Effects, 3S, Membrane Tissue, 0904/17, RECOVERED/RESOLVED, Home Economics, 6S)-cyclohexane-1, Hypothesis, Dmel_CG7826, cis-1, TAFII-250, TAF250/230, Optical Microscopy, DECREASED, Macroeconomic Factors, Economics, 6-hexol, Induction, TAFII250, Household, Causing, SZ1, Migrant, Theoretical Studies, Decrease, Workers, Phosphoglyceride, HMWK, (3-D-Pro)-Isomer, Lysyl-bradykinin, Dmel_CG7835, Confirmation, Domain, 5R, 4s, Mnb, MNB, Factors, Trial Phase 2/3, Stimulation, Neuroblastomas, 1D-myo-Inositol, Modeling, Phase II/III Trial, COURSE, phase II/III trial, Due To, Low molecular weight growth-promoting factor, AW124434, CG17603, merged with, TAF[[II]], early, Stimulating, meso-Inositol, Easterlin Hypothesis, Horka, SR3-5, Inositide Phospholipids, Base, PH Domains, Fs(3)Horka, anon-EST:Liang-2.39, Microscopy, (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer, Contribute, Remittances, Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, d230, 6-cyclohexanehexol, Math, plasma membrane intrinsic protein 2A, P62, Kininogen-1 heavy chain, Gene, dTAFII250, EfW1, Migrant Workers, Bradykinin Triacetate, L-bradykinin, reduced, dmTAF1, subnumerary, Taf230, integral component of membrane, Studies, GFP 细胞, Experimental Model, Stimulated, DmF2, Next, Inositide Phospholipid, Models, Cyclohexitol, TAF250, lod, Chiro Inositol, Help, Ile-Ser-Bradykinin, Taf200, {Course}, Phospholipid, l(3)s2612, Transients, GFP, Reduction, Nonmigrants, Taf1p, T-kinin, decreased number, Economic Conditions, course, Heightened, Squatter, (6-D-Ser)-Isomer, Optical, Following, Clampings, Bios I, DmelCG10293, region of membrane, (9-D-Arg)-Isomer, Long-Term Effect, Model, TAF, Policy, Economic Policy, membrane, DYRK1, Kininogen-1 light chain, TAF[[II]]250, Inositol Phosphoglyceride, protein complex, clone 2.39, synthesize, More Than, l(3)84Ab, Production, Living Cost, Resolved, Assistance, Consumption, Inositol, p230, Protein, Nomad, whole membrane, TFIID, Dyrk1, Alpha-2-thiol proteinase inhibitor, Resolution, who, Basic, Phosphoinositide, Contributing, transmembrane, TAF[[II]]230, Neuroblastoma, Ins, CC1, Basis, TAF[II]250, Who/How, Membrane, PH Domain, Protein Gene Products, DmelCG17603, Inositol Phospholipid, Remittance, Only, Increase, concentration, joined with, Cost of Living, qkr[93F], Single, assay, coalesced, Assist, Contribution, TAF1extent, IPP2A2, PSP94, Public Sectors, determination, GFP cell, Dambose, Imaging, protein, PtdIns, Bradykinin Diacetate, Bradykinin Acetate, Long Term, 5730420M11Rik, dmTAF[[II]]230, Meat sugar, Membrane Tissues, appendix, Light Microscopy, Mesoinositol, i-inositol, Appendix, 1, 2, CG9614, Min, 3, 4, Kallidin II, 5, Public Enterprise, protein aggregate, Fs(3)Hor, present in fewer numbers in organism, Effect, DmelCG42273, multicellular organismal biosynthetic process, SET, D-myo-Inositol, inosite, single-organism biosynthetic process, DmelCG2684, Migrant Worker, TFIID TAF250, BK, TAF-I, cel, L-Arg-L-Pro-L-Pro-Gly-L-Phe-L-Ser-L-Pro-L-Phe-L-Arg, Simple, membrane region, Public Domains, Nonmigrant, Tissue, L-myo-Inositol, min, mAPC, Hand-Held Microscopy, Constrictions, Arg Pro Pro Gly Phe Ser Pro Phe Arg, NTef2, Transient, (1-D-Arg)-Isomer, Phosphatidyl Inositol, (2-D-Pro)-Isomer, DmelCG4299, AI047805, 2R, Inositol Phospholipids, IGAAD, set, decreased, GPIP4, DmelCG10574, beta-MSP, appendix vermiformis, Hand-Held, High molecular weight kininogen, Squatters, fused to, TL, Long-Term Effects, NICR1047, DmelCG9614, 3S, phapii, Membrane Tissue, dTAF[[II]]230, Papers, (1r, 6S)-cyclohexane-1, completeness, TAF200, Dmel_CG7826, Longterm Effect, StF-IT-1, integral to membrane, cis-1, mSMGP, Light, TAFII-250, TAF250/230, Optical Microscopy, predicted, Fs(3)Sz11, 6-hexol, TAFII250, (5-D-Phe-8-D-Phe)-Isomer, Dm1, Public Domain, Migrant, Domains, Workers, Phosphoglyceride, HMWK, (3-D-Pro)-Isomer, (2-D-Pro-7-D-Pro)-Isomer, Lysyl-bradykinin, Dmel_CG7835, Migrants and Transients, Domain, 5R, 4-phosphatase, 4s, Mnb, MNB, 1L-myo-Inositol, HLA-DR-associated protein II, DI-2, Neuroblastomas, 1D-myo-Inositol, Vermiform Appendix, phosphatidylinositols, I-2Dm, (7-D-Pro)-Isomer, PAP-inositol 1, Low molecular weight growth-promoting factor, CG4299, AW124434, CG17603, 5/4, merged with, TAF[[II]], early, l(3)76BDp, Hand Held Microscopy, I-2PP1, Phosphoinositides, meso-Inositol, Sector, pipe-ST2, TAF-IBETA, Taf250, SR3-5, Horka, Inositide Phospholipids, GP17, Kallidin I, 6-HEXAHYDROXY-CYCLOHEXANE, CG2684, Vermiform, Fs(3)Horka, Cytosols, Migrants, TAF-Ibeta, Microscopy, fused, (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer, i2pp2a, TAF230, RPPGFSPFR, Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, Williams-Fitzgerald-Flaujeac factor, Inositide, d230, Sectors, 6-cyclohexanehexol, Effects, Fitzgerald factor, Phosphatidylinositol, number, Kininogen-1 heavy chain, Gene, dTAFII250, Copyrights, protein-containing complex, EfW1, presence, Migrant Workers, PHAPII, CG7826, Bradykinin Triacetate, L-bradykinin, reduced, dmTAF1, Taf230, subnumerary, integral component of membrane, GFP 细胞, CG7835, Gene Products, CG42273, Phosphatidyl, DmF2, Inositide Phospholipid, Enterprises, TAF250, Cyclohexitol, lod, Chiro Inositol, Taf200, Ile-Ser-Bradykinin, dTAF[[II]]250, Phospholipid, Longterm, cell, Tissues, ligand, Transients, GFP, ipp2a2, 2pp2a, Nonmigrants, Taf1p, Bradykinin, T-kinin, GCDFP15, Long-Term, scHAL2 analogous 3, decreased number, Worker, Public Enterprises, CG10574, apex of cecum, Squatter, dTAF250, (6-D-Ser)-Isomer, Table, Abstract, Optical, 2PP2A, taf-ibeta, Clampings, N1E-115, Bios I, dSET, dSet, region of membrane, (9-D-Arg)-Isomer, Long-Term Effect, species, PIP, TAF, Enterprise, Bradykinin Hydrochloride, HEL20, (8-D-Phe)-Isomer, membrane, DYRK1, TAF[[II]]250, Kininogen-1 light chain, (3-D-Pro-7-D-Pro)-Isomer, Inositol Phosphoglyceride, PAR-interacting protein, apex of caecum, protein complex, synthesize, Proteins, igaad, 5-trans-4, l(3)84Ab, Phosphoglycerides, BG:DS00004.13, Cell, group, 3.1.3.7, dTAF230, Inositol, GCDFP-15, count in organism, native protein, Inositol Phosphoglycerides, I-2PP2A, Public, p230, Simple Microscopy, Clamping, chemical analysis, Dm I-2, Protein, Long Term Effects, I2PP2A, Nomad, whole membrane, TAF[[II]]250/230, TFIID, NB, Dyrk1, Data Base, Alpha-2-thiol proteinase inhibitor, Taf[[II]]250, AU020952, Phosphoinositide, transmembrane, TAF[[II]]230, Phospholipids, ensemble, Neuroblastoma, Compound Microscopy, Ins, CC1, Chiro-Inositol, (5-D-Phe)-Isomer, Myoinositol, TAF[II]250, Membrane, Lds, Bisphosphate 3'-nucleotidase 1, Longterm Effects, ME-IV, Protein Gene Products, Gene Proteins, dSET/TAF-Ibeta, inositols, 2610030F17Rik, DmelCG17603, Inositol Phospholipid, concentration, Compound, Pipe, joined with, Nomads, Public., assay, AA407739, PI, coalesced, TAF1Phosphoinositide, Inositide, Inositol Phosphoglyceride, Phospholipid, determination, Activation, Phospholipids, Inositol., Activated, Phosphatidylinositol, Phosphoglycerides, PtdIns, Phosphatidyl Inositol, Phosphoinositides, Inositol Phospholipids, Inositol, Inositol Phospholipid, Inositol Phosphoglycerides, chemical analysis, Inositide Phospholipids, Phosphatidyl, assay, Activate, Phosphoglyceride, activate, Inositide PhospholipidfalseXu2003 - Phosphoinositide turnover
Xu2003 - Phosphoinositide turnover
The model reproduces the percentage change of PIP_PM, PIP2_PM and IP3_Cyt as depicted in Figure 1 of the paper. The model also contains the equations for the analysis of PH-GFP experiments, however the initial value of PH_GFP has been set to zero to more accurately reproduce Figure 1. The units of cytosolic species are given in molecules/um^3. In order to convert them to uM, divide the concentration by 602. For the analysis of PH_GFP experiments, one should plug in the values of PH_GFP, IP3_PHGFP and PIP2_PHGFP from Table AI in the appendix. The model was successfully tested on MathSBML.
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This model is described in the article:
Kinetic analysis of receptor-activated phosphoinositide turnover.
Xu C, Watras J, Loew LM.
J. Cell Biol. 2003 May; 161(4): 779-791
Abstract:
We studied the bradykinin-induced changes in phosphoinositide composition of N1E-115 neuroblastoma cells using a combination of biochemistry, microscope imaging, and mathematical modeling. Phosphatidylinositol-4,5-bisphosphate (PIP2) decreased over the first 30 s, and then recovered over the following 2-3 min. However, the rate and amount of inositol-1,4,5-trisphosphate (InsP3) production were much greater than the rate or amount of PIP2 decline. A mathematical model of phosphoinositide turnover based on this data predicted that PIP2 synthesis is also stimulated by bradykinin, causing an early transient increase in its concentration. This was subsequently confirmed experimentally. Then, we used single-cell microscopy to further examine phosphoinositide turnover by following the translocation of the pleckstrin homology domain of PLCdelta1 fused to green fluorescent protein (PH-GFP). The observed time course could be simulated by incorporating binding of PIP2 and InsP3 to PH-GFP into the model that had been used to analyze the biochemistry. Furthermore, this analysis could help to resolve a controversy over whether the translocation of PH-GFP from membrane to cytosol is due to a decrease in PIP2 on the membrane or an increase in InsP3 in cytosol; by computationally clamping the concentrations of each of these compounds, the model shows how both contribute to the dynamics of probe translocation.
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2024-08-212024-09-022006-11-09BIOMD0000000075OPB_01072SBO:0000216SBO:0000182SBO:0000170SBO:0000179map04070CHEBI:18348CHEBI:28874CHEBI:16595CHEBI:26034CHEBI:18035CHEBI:30212MODEL3095606944BIOMD0000000075GO:0046488GO:0005576GO:0005886GO:0005622GO:0031965GO:000563410090IPR011584IPR0018493.1.4.1112771127PATO:0002355BTO:0000931Q8K4S1