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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 occurrences1001430

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • Ajay_Bhalla_
    2004_Feedback_
    Tuning
  • 78Network
    Shared_Object_Ajay_Bhalla_2004_Feedback_Tuning PKC PLA2 
    PLCbeta Gq MAPK 
    Ras EGFR Sos 
    PLC_g CaMKII CaM 
    PP1 PP2B PKA 
    AC 
    This model is taken from Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80. This is the feedback model from Figure 8a.

    GTP-Ras acting as a Molecule in  
    Ajay_Bhalla_2004_Feedback_Tuning Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    GTP-Ras
  • Ajay_Bhalla_
    2004_Feedback_
    Tuning

    Accession No. : 78
  • Ras
    Pathway No. : 353
    01.5No
    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_2004_Feedback_Tuning Network
    Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    GAP  /
    GAP-inact-ras
  • Ajay_Bhalla_
    2004_Feedback_
    Tuning

    Accession No. : 78
  • Ras
    Pathway No. : 353
    1.01039104explicit 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_2004_Feedback_Tuning Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1GEF-Gprot-bg  /
    GEF-bg_act-ras
  • Ajay_Bhalla_
    2004_Feedback_
    Tuning

    Accession No. : 78
  • Ras
    Pathway No. : 353
    0.5050510.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
        Kinetics based on the activation of Gq by the receptor complex in the Gq model (in turn based on the Mahama and Linderman model) k1 = 2e-5, k2 = 1e-10, k3 = 10 (I do not know why they even bother with k2). Lets put k1 at 2e-6 to get a reasonable equilibrium More specific values from, eg.g: Orita et al JBC 268(34) 25542-25546 from rasGRF and smgGDS: k1=3.3e-7; k2 = 0.08, k3 = 0.02
    2GEF*  /
    GEF*-act-ras
  • Ajay_Bhalla_
    2004_Feedback_
    Tuning

    Accession No. : 78
  • Ras
    Pathway No. : 353
    0.5050510.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
        Kinetics same as GEF-bg-act-ras
    3CaM-GEF  /
    CaM-GEF-act-ras
  • Ajay_Bhalla_
    2004_Feedback_
    Tuning

    Accession No. : 78
  • Ras
    Pathway No. : 353
    0.5050510.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
        Kinetics same as GEF-bg_act-ras
    4Shc*.Sos.Grb2  /
    Sos.Ras_GEF
  • Ajay_Bhalla_
    2004_Feedback_
    Tuning

    Accession No. : 78
  • Shared_Object_
    Ajay_Bhalla_
    2004_Feedback_
    Tuning

    Pathway No. : 347
  • 0.5050510.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
       

    GTP-Ras acting as a Substrate in a reaction in  
    Ajay_Bhalla_2004_Feedback_Tuning 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_
    2004_Feedback_
    Tuning

    Accession No. : 78
  • Shared_Object_
    Ajay_Bhalla_
    2004_Feedback_
    Tuning

    Pathway No. : 347
  • 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_
    2004_Feedback_
    Tuning

    Accession No. : 78
  • Ras
    Pathway No. : 353
    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_
    2004_Feedback_
    Tuning

    Accession No. : 78
  • Shared_Object_
    Ajay_Bhalla_
    2004_Feedback_
    Tuning

    Pathway No. : 347
  • 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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