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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 occurrences1001420

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
EGFR_MAPK58Network
Shared_Object_EGFR_MAPK MAPK Ras 
EGFR Sos 
Model of MAPK activation by EGFR in the synapse. Demonstration programs using this model are available here.
Primary citation:Bhalla US. Biophys J. (2004) 87(2):745-53.

GTP-Ras acting as a Molecule in  
EGFR_MAPK Network
NameAccession NamePathway NameInitial Conc.
(uM)
Volume
(fL)
Buffered
GTP-RasEGFR_MAPK
Accession No. : 58
Ras
Pathway No. : 231
01000No
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  
EGFR_MAPK Network
Enzyme Molecule /
Enzyme Activity
Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
GAP  /
GAP-inact-ras
EGFR_MAPK
Accession No. : 58
Ras
Pathway No. : 231
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  
EGFR_MAPK Network
 Enzyme Molecule /
Enzyme Activity
Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
1GEF-Gprot-bg  /
GEF-bg_act-ras
EGFR_MAPK
Accession No. : 58
Ras
Pathway No. : 231
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
EGFR_MAPK
Accession No. : 58
Ras
Pathway No. : 231
0.5050510.024explicit E-S complexSubstrate
GDP-Ras

Product
GTP-Ras
    Kinetics same as GEF-bg-act-ras
3CaM-GEF  /
CaM-GEF-act-ras
EGFR_MAPK
Accession No. : 58
Ras
Pathway No. : 231
0.5050510.024explicit E-S complexSubstrate
GDP-Ras

Product
GTP-Ras
    Kinetics same as GEF-bg_act-ras
4Shc*.Sos.Grb2  /
Sos.Ras_GEF
EGFR_MAPK
Accession No. : 58
  • Shared_Object_
    EGFR_MAPK

    Pathway No. : 229
  • 0.5050510.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras

    GTP-Ras acting as a Substrate in a reaction in  
    EGFR_MAPK 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-crafEGFR_MAPK
    Accession No. : 58
  • Shared_Object_
    EGFR_MAPK

    Pathway No. : 229
  • 24
    (uM^-1 s^-1)
    0.5
    (s^-1)
    Kd(bf) = 0.0208(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 (I don't....
    2
  • Ras-intrinsic-GT
    Pase
  • EGFR_MAPK
    Accession No. : 58
    Ras
    Pathway No. : 231
    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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