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Molecule Parameter List for GDP-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
GDP-Ras participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1003101

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)

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

    Accession No. : 79
  • Ras
    Pathway No. : 367
    0.5125.7No
    GDP bound form. See Rosen et al Neuron 12 1207-1221 June 1994. the activation loop is based on Boguski and McCormick Nature 366 643-654 93 Assume Ras is present at about the same level as craf-1, 0.2 uM. Hallberg et al JBC 269:6 3913-3916 1994 estimate upto 5-10% of cellular Raf is assoc with Ras. Given that only 5-10% of Ras is GTP-bound, we need similar amounts of Ras as Raf.

    GDP-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
    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

    GDP-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
    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.

    GDP-Ras acting as a Product 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
  • 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



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