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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
  • mkp1_feedback_
    effects
  • 4Network
    Shared_Object_mkp1_feedback_effects Sos PKC 
    MAPK PLA2 Ras 
    PDGFR 
    This is a network involving the MAPK-PKC feedback loop with input from the PDGFR in the synapse. The distinctive feature of this model is that it includes MKP-1 induction by MAPK, and the consequent inhibitory regulation of MAPK and the feedback loop. Lots of interesting dynamics arise from this. This link provides supplementary material for the paper Bhalla US et al. Science (2002) 297(5583):1018-23. In the form of several example simulations and demos for the figures in the paper.

    Raf*-GTP-Ras acting as a Molecule in  
    mkp1_feedback_effects Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    Raf*-GTP-Ras
  • mkp1_feedback_
    effects

    Accession No. : 4
  • MAPK
    Pathway No. : 35
    01000No
    This is the main activated form of craf. It requires binding to ras for activation, but the presence of the phosphorylation increases this binding. See Leevers 1994 Nature 369:411-414 and Hallberg et al 1994 JBC 269(6):3913-3916

    Raf*-GTP-Ras acting as an Enzyme in  
    mkp1_feedback_effects Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1Raf*-GTP-Ras /
    Raf*-GTP-Ras.1
  • mkp1_feedback_
    effects

    Accession No. : 4
  • MAPK
    Pathway No. : 35
    0.1590910.1054explicit 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. They report Km for MAPKK of 0.8 uM. and a Vmax of ~500 fm/min/ug. These parms cannot reach the observed 4X stimulation of MAPK. So we increase the affinity, ie, raise k1 5x to 5.5e-6 which is equivalent to 5-fold reduction in Km to about 0.16. This is, of course, dependent on the amount of MAPKK present.
    2Raf*-GTP-Ras /
    Raf*-GTP-Ras.2
  • mkp1_feedback_
    effects

    Accession No. : 4
  • MAPK
    Pathway No. : 35
    0.1590910.1054explicit E-S complexSubstrate
    MAPKK-ser

    Product
    MAPKK*
        Same kinetics as other c-raf activated forms. See Force et al PNAS 91 1270-1274 1994.

    Raf*-GTP-Ras acting as a Product in a reaction in  
    mkp1_feedback_effects 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
  • mkp1_feedback_
    effects

    Accession No. : 4
  • Shared_Object_
    mkp1_feedback_
    effects

    Pathway No. : 32
  • 60
    (uM^-1 s^-1)
    0.5
    (s^-1)
    Kd(bf) = 0.0083(uM)-Substrate
    GTP-Ras
    craf-1*

    Product
    Raf*-GTP-Ras
    Assume binding is fast and limited only by available Ras*. 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 about 1e-4, giving a Kf of 60 for Kb of 0.5 and a tau of approx 2 sec. Based on: Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414. Also see Koide et al 1993 PNAS USA 90(18):8683-8686



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