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Molecule Parameter List for GTP-Ras

The statistics table lists the distribution of a molecule acting either as a substrate, product, enzyme or as a molecule within the network.
The text color of a molecule is highlighted by color.
Statistics
GTP-Ras participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1001330

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • Ajay_Bhalla_
    2007_Bistable
  • 79Network
    Shared_Object_Ajay_Bhalla_2007_Bistable PKC PLA2 
    MAPK Ras CaM 
    This is a model of ERKII signaling which is bistable due to feedback. The feedback occurs through ERKII phosphorylation of phospholipase A2 (PLA2), leading to increased production of arachidonic acid (AA), which activates protein kinase C (PKC) which activates c-Raf which is upstream of ERKII.
    The model is a highly simplified variant of more detailed bistable models of MAPK signaling (Bhalla US, Iyengar R. Science. 1999 Jan 15;283(5400):381-7, Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80)

    GTP-Ras acting as a Molecule in  
    Ajay_Bhalla_2007_Bistable Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    GTP-Ras
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Ras
    Pathway No. : 367
    0125.7No
    Only a very small fraction (7% unstim, 15% stim) of ras is GTP-bound. Gibbs et al JBC 265(33) 20437

    GTP-Ras acting as a Substrate for an Enzyme in  
    Ajay_Bhalla_2007_Bistable Network
    Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    GAP  /
    GAP-inact-ras
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Ras
    Pathway No. : 367
    1.0104104explicit E-S complexSubstrate
    GTP-Ras

    Product
    GDP-Ras
    From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) 5 Nov 2002: Changed ratio term to 4 from 100. Now we have k1=8.25e-5; k2=40, k3=10. k3 is still rate-limiting.

    GTP-Ras acting as a Product of an Enzyme in  
    Ajay_Bhalla_2007_Bistable Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1inact-GEF  /
  • basal_GEF_
    activity
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Ras
    Pathway No. : 367
    10.10140.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
       
    2GEF*  /
    GEF*-act-ras
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Ras
    Pathway No. : 367
    0.505050.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
        Kinetics same as GEF-bg-act-ras
    3CaM-GEF  /
    CaM-GEF-act-ras
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Ras
    Pathway No. : 367
    0.5050310.14explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
        Kinetics same as GEF-bg_act-ras

    GTP-Ras acting as a Substrate in a reaction in  
    Ajay_Bhalla_2007_Bistable Network
    Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated. Kd for higher order reaction are not consider.
     NameAccession NamePathway NameKfKbKdtauReagents
    1Ras-act-craf
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Shared_Object_
    Ajay_Bhalla_
    2007_Bistable

    Pathway No. : 363
  • 9.9999
    (uM^-1 s^-1)
    0.5
    (s^-1)
    Kd(bf) = 0.05(uM)-Substrate
    GTP-Ras
    craf-1*

    Product
    Raf*-GTP-Ras
      Assume the binding is fast and limited only by the amount of Ras* available. So kf=kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 May 16, 2003 Changed Ras and Raf to synaptic levels, an increase of about 2x for each. To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold to 10.
    2
  • Ras-intrinsic-GT
    Pase
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Ras
    Pathway No. : 367
    0.0001
    (s^-1)
    0
    (s^-1)
    --Substrate
    GTP-Ras

    Product
    GDP-Ras
      This is extremely slow (1e-4), but it is significant as so little GAP actually gets complexed with it that the total GTP turnover rises only by 2-3 X (see Gibbs et al, JBC 265(33) 20437-20422) and Eccleston et al JBC 268(36) 27012-27019 kf = 1e-4
    3
  • Ras-act-unphosph
    -raf
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Shared_Object_
    Ajay_Bhalla_
    2007_Bistable

    Pathway No. : 363
  • 6
    (uM^-1 s^-1)
    1
    (s^-1)
    Kd(bf) = 0.1667(uM)-Substrate
    GTP-Ras
    craf-1

    Product
    Raf-GTP-Ras
      18 May 2003. This reaction is here to provide basal activity for MAPK as well as the potential for direct EGF stimulus without PKC activation. Based on model from FB/fb28c.g: the model used for MKP-1 turnover. The rates there were constrained by basal activity values.



    Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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