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Molecule Parameter List for Raf*-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
Raf*-GTP-Ras participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1020001

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • Ajay_Bhalla_
    2004_PKM_Tuning
  • 76Network
    PKC Shared_Object_Ajay_Bhalla_2004_PKM_tuning PLA2 
    PLCbeta Gq MAPK 
    Ras EGFR Sos 
    PLC_g CaMKII CaM 
    PP1 PP2B PKA 
    AC PKM 
    This model is taken from the Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80. This is the reference feedforward model from Figure 8a.

    Raf*-GTP-Ras acting as a Molecule in  
    Ajay_Bhalla_2004_PKM_Tuning Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    Raf*-GTP-Ras
  • Ajay_Bhalla_
    2004_PKM_Tuning

    Accession No. : 76
  • MAPK
    Pathway No. : 317
    01.5No

    Raf*-GTP-Ras acting as an Enzyme in  
    Ajay_Bhalla_2004_PKM_Tuning Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1Raf*-GTP-Ras /
    Raf*-GTP-Ras.1
  • Ajay_Bhalla_
    2004_PKM_Tuning

    Accession No. : 76
  • MAPK
    Pathway No. : 317
    0.1590940.34explicit E-S complexSubstrate
    MAPKK

    Product
    MAPKK-ser
        Kinetics are the same as for the craf-1* activity, ie., k1=1.1e-6, k2=.42, k3 =0.105 These are based on Force et al PNAS USA 91 1270-1274 1994. These parms cannot reach the observed 4X stim of MAPK. So lets increase the affinity, ie, raise k1 10X to 1.1e-5 Lets take it back down to where it was. Back up to 5X: 5.5e-6
    2Raf*-GTP-Ras /
    Raf*-GTP-Ras.2
  • Ajay_Bhalla_
    2004_PKM_Tuning

    Accession No. : 76
  • MAPK
    Pathway No. : 317
    0.1590940.34explicit E-S complexSubstrate
    MAPKK-ser

    Product
    MAPKK*
        Same kinetics as other c-raf activated forms. See Force et al PNAS 91 1270-1274 1994. k1 = 1.1e-6, k2 = .42, k3 = 1.05 raise k1 to 5.5e-6

    Raf*-GTP-Ras acting as a Product in a reaction in  
    Ajay_Bhalla_2004_PKM_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
    Ras-act-craf
  • Ajay_Bhalla_
    2004_PKM_Tuning

    Accession No. : 76
  • Shared_Object_
    Ajay_Bhalla_
    2004_PKM_tuning

    Pathway No. : 312
  • 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.



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