BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000899?filename=Ota2015_GDI-integrated.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000899?filename=Ota2015_GDI-integrated.cpshttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000899?filename=Ota2015_GDI-integrated.sedmlprimaryOK200Johannes MeyerManually curatedordinary differential equation modelL2V4https://www.ebi.ac.uk/biomodels/BIOMD000000089925628036falseBioModelsSBMLModelsOta2015 Positive regulation of Rho GTPase activity by RhoGDIs as a result of their direct interaction with GAPs (GDI integrated)2015MODEL1912170003Ota T, Maeda M, Okamoto M, Tatsuka MOta T25628036,
Rho GTPases function as molecular switches in many different signaling pathways and control a wide range of cellular processes. Rho GDP-dissociation inhibitors (RhoGDIs) regulate Rho GTPase signaling and can function as both negative and positive regulators. The role of RhoGDIs as negative regulators of Rho GTPase signaling has been extensively investigated; however, little is known about how RhoGDIs act as positive regulators. Furthermore, it is unclear how this opposing role of GDIs influences the Rho GTPase cycle. We constructed ordinary differential equation models of the Rho GTPase cycle in which RhoGDIs inhibit the regulatory activities of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) by interacting with them directly as well as by sequestering the Rho GTPases. Using this model, we analyzed the role of RhoGDIs in Rho GTPase signaling.The model constructed in this study showed that the functions of GEFs and GAPs are integrated into Rho GTPase signaling through the interactions of these regulators with GDIs, and that the negative role of GDIs is to suppress the overall Rho activity by inhibiting GEFs. Furthermore, the positive role of GDIs is to sustain Rho activation by inhibiting GAPs under certain conditions. The interconversion between transient and sustained Rho activation occurs mainly through changes in the affinities of GDIs to GAPs and the concentrations of GAPs.RhoGDIs positively regulate Rho GTPase signaling primarily by interacting with GAPs and may participate in the switching between transient and sustained signals of the Rho GTPases. These findings enhance our understanding of the physiological roles of RhoGDIs and Rho GTPase signaling.. null, 9.
Division of Tumor Biology, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada 920-0293, Ishikawa, Japan. takahide@kanazawa-med.ac.jp.johannes.p.meyer@gmail.comEMBL-EBIBIOMD0000000899<h4>Background</h4>Rho GTPases function as molecular switches in many different signaling pathways and control a wide range of cellular processes. Rho GDP-dissociation inhibitors (RhoGDIs) regulate Rho GTPase signaling and can function as both negative and positive regulators. The role of RhoGDIs as negative regulators of Rho GTPase signaling has been extensively investigated; however, little is known about how RhoGDIs act as positive regulators. Furthermore, it is unclear how this opposing role of GDIs influences the Rho GTPase cycle. We constructed ordinary differential equation models of the Rho GTPase cycle in which RhoGDIs inhibit the regulatory activities of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) by interacting with them directly as well as by sequestering the Rho GTPases. Using this model, we analyzed the role of RhoGDIs in Rho GTPase signaling.<h4>Results</h4>The model constructed in this study showed that the functions of GEFs and GAPs are integrated into Rho GTPase signaling through the interactions of these regulators with GDIs, and that the negative role of GDIs is to suppress the overall Rho activity by inhibiting GEFs. Furthermore, the positive role of GDIs is to sustain Rho activation by inhibiting GAPs under certain conditions. The interconversion between transient and sustained Rho activation occurs mainly through changes in the affinities of GDIs to GAPs and the concentrations of GAPs.<h4>Conclusions</h4>RhoGDIs positively regulate Rho GTPase signaling primarily by interacting with GAPs and may participate in the switching between transient and sustained signals of the Rho GTPases. These findings enhance our understanding of the physiological roles of RhoGDIs and Rho GTPase signaling.Positive regulation of Rho GTPase activity by RhoGDIs as a result of their direct interaction with GAPs.Ota Takahide T, Maeda Masayo M, Okamoto Mayumi M, Tatsuka Masaaki Mstimulation of Rac GTPase activity, GDI., upregulation of Rho GTPase activity, up regulation of Ran GTPase activity, upregulation of Rap GTPase activity, positive regulation of Rab GTPase activity, upregulation of Ras GTPase activity, stimulation of Ras GTPase activity, stimulation of Ral GTPase activity, positive regulation of Ral GTPase activity, stimulation of GTPase activity, up-regulation of GTPase activity, upregulation of Cdc42 GTPase activity, stimulation of ARF GTPase activity, Prgs, stimulation of Cdc42 GTPase activity, upregulation of GTPase activity, stimulation of Rap GTPase activity, up-regulation of Rap GTPase activity, up-regulation of Ras GTPase activity, positive regulation of Ras GTPase activity, up-regulation of ARF GTPase activity, up regulation of Rab GTPase activity, positive regulation of ARF GTPase activity, upregulation of Ral GTPase activity, positive regulation of Rap GTPase activity, upregulation of Rac GTPase activity, stimulation of Ran GTPase activity, up regulation of Cdc42 GTPase activity, up regulation of GTPase activity, up regulation of Rho GTPase activity, up regulation of Rac GTPase activity, activation of GTPase activity, positive regulation of Rho GTPase activity, upregulation of Rab GTPase activity, upregulation of Ran GTPase activity, up-regulation of Rac GTPase activity, up-regulation of Ral GTPase activity, Gaps, up regulation of Rap GTPase activity, up regulation of Ras GTPase activity, up regulation of ARF GTPase activity, positive regulation of Rac GTPase activity, upregulation of ARF GTPase activity, up-regulation of Rab GTPase activity, up-regulation of Cdc42 GTPase activity, up regulation of Ral GTPase activity, positive regulation of Ran GTPase activity, up-regulation of Rho GTPase activity, stimulation of Rho GTPase activity, positive regulation of Cdc42 GTPase activity, stimulation of Rab GTPase activity, up-regulation of Ran GTPase activityprojections, Ghrfr, dlmo, Activity, DLMO, 2410041A17Rik, ACTG, ACTE, Rho A, fond, GTPase-Activating Protein, fs(1)M34, sci, CycEI, Act5, csp2, hdp-a, l(1)G0420, DmelCG12051, dLmo, dLMO, Readability, DmelCG1004, Ccne, rho-1, Roles, Reversing Factors, symptoms, Concepts, HOW, How, HEL-176, CG4601, DRho, AAF01186, 8416, l(3)j5D5, 24B, Dmrho, A, C, opsin-2, GDP Dissociation Stimulators, cyt5C, Migrant Worker, reference sample, GDP Exchange, DHO, Nonmigrant, DMRHO, stru, CG18572, l(3)S053606, CG10293, Transient, Gaps, rhoA, Rho1, RHO1, GDP-GTP Exchange Protein, retention, DmelCG8416, Bd, l(3)j5B5, Dlmo, act 42A, signaling process, papilla, GDP GTP Reversing Factors, rho1, Role Concepts, Ac5C, CG4027, Squatters, ACT, Act, fliH, single organism signaling, screening, 0904/17, anatomical protrusion, l(1)G0330, wide/broad, Rho-1, DmRHO-A, Actin/BAP47, CTE-II, RHOb, AACT, GDP-GTP Reversing, lamina, CTE-IIa, CG1004, HSC0013, flanges, act, Exchange Factors, Ach1, hBACH, ACH1, lit, LACH1, Cyc E, br37, results, Dm Rho1, act42A, rhom, GIG25, RhoN19, Role Concept, BG:DS07108.3, Prgs, Alpha-1-antichymotrypsin His-Pro-less, Su(b), SZ1, AFFX-Dros-ACTIN_M_r_at, Migrant, RhoA, ve, shelf, GDP GTP Exchange Protein, Role, DFNA26, RHOM, RhoM, actin, Workers, RHOHP1, LACH, l(2)05206, DFNA20, GAT, activation, Migrants and Transients, little, Ptd, DmelCG4027, Factors, maintenance of localization, AI326383, D-Rho1, shelves, l(1)G0117, Ve, CG8416, signs, Actin, RHO, Rho, projection, ridge, beta-actin/Bap47, DMRHOa, DMRHOb, GTPase Activating Proteins, l(1)G0486, l(1)G0245, wide, actin5C, l35Dd, l(1)G0009, rhomboid/veinlet, spine, ACTL3, Lach1, Lmo, LMO, ARHD, anon-EST:Liang-2.39, Migrants, hdp, Guanine-Nucleotide-Releasing Factor, rho, BACH, l(1)Ab, Act5c, Dmelrho, biological signaling, l(1)G0010, cycline, DRORHO, lamellae, P62, DmcyclinE, Arhd, GDP, ACT5C, GDP-GTP Reversing Factors, CG12051, cycE, broad, Serpin A3, GTPase Activating Protein, Bach, process of organ, Rho GTPase, l(2)br37, Migrant Workers, CYCLE, protrusion, cdi7, lamella, l(1)G0025, cyclinE, DRhoA, GDP-GTP, dttg, GAP Proteins, Cdi7, CDI7, Cell growth-inhibiting gene 24|25 protein, CG6500, Guanine Nucleotide Releasing Factors, study, dRhoA, act5C, CYCE, l(3)s2612, beadex/dLMO, DmelCG3938, BRWS2, CyclE, Transients, inhibiteur, 3938, Nonmigrants, ridges, DRho1, DmcycE, Worker, DrhoA, OPN2, fs(1)829, l(2)k05007, Squatter, anon-EST:fe2D2, Act42a, dm-cycE, inhibidor, 1700027G07Rik, RhoHP1, DmelCG18572, transient structure, Drho1, DmelCG10293, Guanine Nucleotide Exchange Factor, dRho1, T11, laminae, Act-5C, Cte-II, Controlled, DmelCG6500, l(1)G0177, signalling., inhibitors, GDP Dissociation Factor, 42A, Rho kinase, Controlling, CPS, findings, clone 2.39, l(2)52Fa, anatomical process, iks, GAP Protein, dJ393D12.2, inhibitor, function, l(2)k02107b, qkr, l(3)S090417, Concept, CAD, l(2)k02514, DmCycE, beta-actin, KH93F, M32055, Nomad, Act42, background, CyeE, ACTA3, dnRho, flange, organ process, who, l(1)G0079, l(2)k02602, storage, PYR1, VSCM, l(2)35Dd, act 5C, E3.10/J3.8, Who/How, Guanine Nucleotide Releasing Factor, Understanding, introduction, signalling, hld, processes, process, D-CycE, signalling process, Nomads, qkr[93F], processus, DRORUD, BAP47, ACTSG, sequestering, n(2)k07236, CG3938, Bap47, General activity, Actin5C, GDP Exchange FactorsDmelrho, dlmo, biological signaling, cycline, DRORHO, DLMO, Rho A, DmcyclinE, fond, GTPase-Activating Protein, Arhd, GDP, GDP-GTP Reversing Factors, cycE, CycEI, GTPase Activating Protein, Rho GTPase, l(2)br37, CYCLE, hdp-a, cdi7, dLmo, dLMO, DmelCG1004, Ccne, cyclinE, DRhoA, GDP-GTP, rho-1, Roles, dttg, GAP Proteins, Reversing Factors, Cdi7, CDI7, Concepts, CG6500, DRho, AAF01186, 8416, Dmrho, Guanine Nucleotide Releasing Factors, dRhoA, opsin-2, GDP Dissociation Stimulators, CYCE, beadex/dLMO, GDP Exchange, DmelCG3938, CyclE, DMRHO, 3938, DRho1, DmcycE, Gaps, rhoA, Rho1, RHO1, GDP-GTP Exchange Protein, retention, DrhoA, OPN2, DmelCG8416, l(2)k05007, Bd, dm-cycE, Dlmo, RhoHP1, GDP GTP Reversing Factors, signaling process, rho1, Role Concepts, Drho1, Guanine Nucleotide Exchange Factor, dRho1, fliH, single organism signaling, DmelCG6500, signalling., GDP Dissociation Factor, Rho kinase, Rho-1, DmRHO-A, l(2)52Fa, RHOb, GDP-GTP Reversing, iks, GAP Protein, CG1004, HSC0013, Exchange Factors, l(2)k02107b, Cyc E, br37, Dm Rho1, Concept, rhom, RhoN19, l(2)k02514, Role Concept, DmCycE, BG:DS07108.3, Prgs, RhoA, ve, GDP GTP Exchange Protein, Role, RHOM, RhoM, CyeE, RHOHP1, l(2)05206, dnRho, Ptd, l(2)k02602, Factors, maintenance of localization, AI326383, D-Rho1, storage, Ve, l(2)35Dd, CG8416, E3.10/J3.8, RHO, Rho, Guanine Nucleotide Releasing Factor, DMRHOa, DMRHOb, GTPase Activating Proteins, hld, D-CycE, l35Dd, signalling process, rhomboid/veinlet, Lmo, LMO, ARHD, hdp, Guanine-Nucleotide-Releasing Factor, sequestering, rho, n(2)k07236, CG3938, GDP Exchange Factorsstimulation of Rac GTPase activity, upregulation of Rho GTPase activity, up regulation of Ran GTPase activity, upregulation of Rap GTPase activity, positive regulation of Rab GTPase activity, upregulation of Ras GTPase activity, stimulation of Ras GTPase activity, stimulation of Ral GTPase activity, positive regulation of Ral GTPase activity, stimulation of GTPase activity, up-regulation of GTPase activity, upregulation of Cdc42 GTPase activity, stimulation of ARF GTPase activity, Prgs, stimulation of Cdc42 GTPase activity, upregulation of GTPase activity, stimulation of Rap GTPase activity, up-regulation of Rap GTPase activity, up-regulation of Ras GTPase activity, positive regulation of Ras GTPase activity, up-regulation of ARF GTPase activity, up regulation of Rab GTPase activity, positive regulation of ARF GTPase activity, upregulation of Ral GTPase activity, positive regulation of Rap GTPase activity, upregulation of Rac GTPase activity, stimulation of Ran GTPase activity, up regulation of Cdc42 GTPase activity, up regulation of GTPase activity, Gaps., up regulation of Rho GTPase activity, up regulation of Rac GTPase activity, activation of GTPase activity, positive regulation of Rho GTPase activity, upregulation of Rab GTPase activity, upregulation of Ran GTPase activity, up-regulation of Rac GTPase activity, up-regulation of Ral GTPase activity, up regulation of Rap GTPase activity, up regulation of Ras GTPase activity, up regulation of ARF GTPase activity, positive regulation of Rac GTPase activity, upregulation of ARF GTPase activity, up-regulation of Rab GTPase activity, up-regulation of Cdc42 GTPase activity, up regulation of Ral GTPase activity, positive regulation of Ran GTPase activity, up-regulation of Rho GTPase activity, stimulation of Rho GTPase activity, positive regulation of Cdc42 GTPase activity, stimulation of Rab GTPase activity, up-regulation of Ran GTPase activityfalseOta2015 - Positive regulation of Rho GTPase activity by RhoGDIs as a result of their direct interaction with GAPs (GDI integrated)
This is a ordinary differential equation mathematical model describing the Rho GTPase cycle in which Rho GDP-dissociation inhibitors (RhoGDIs) inhibit the regulatory activities of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) by interacting with them directly as well as by sequestering the Rho GTPases. The model was constructed with the intent of analyzing the role of RhoGDIs in Rho GTPase signaling.
2019-12-172019-12-172019-12-17BIOMD0000000899SBO:0000177SBO:0000180SBO:000017925628036C12508C45329C64382C16702CHEBI:352249606