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Molecule Parameter List for Sos.Grb2

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
Sos.Grb2 participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1000011

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • MAPK-bistability
    -fig1c
  • 35Network
    Shared_Object_MAPK-bistability-fig1c Sos PKC 
    MAPK PLA2 Ras 
    PDGFR 
    Model for figure 1c in Bhalla US et al. Science (2002) 297(5583):1018-23.
    The demo for this figure is available here. This synaptic signaling model is without the MKP-1 feedback, so it is bistable and remains so over long periods.

    Sos.Grb2 acting as a Molecule in  
    MAPK-bistability-fig1c Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    Sos.Grb2
  • MAPK-bistability
    -fig1c

    Accession No. : 35
  • Sos
    Pathway No. : 180
    01000No
    For simplicity I treat the activation of Sos as involving a single complex comprising Sos, Grb2 and Shc*. This is reasonably documented: Sasaoka et al 1994 JBC 269(51):32621-5 Chook et al JBC 1996 271(48):30472

    Sos.Grb2 acting as a Substrate in a reaction in  
    MAPK-bistability-fig1c 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
  • Shc_bind_
    Sos.Grb2
  • MAPK-bistability
    -fig1c

    Accession No. : 35
  • Sos
    Pathway No. : 180
    0.5
    (uM^-1 s^-1)
    0.1
    (s^-1)
    Kd(bf) = 0.2(uM)-Substrate
    SHC*
    Sos.Grb2

    Product
    Shc*.Sos.Grb2
    Sasaoka et al JBC 269:51 pp 32621 1994, table on pg 32623 indicates that this pathway accounts for about 50% of the GEF activation. (88% - 39%). Error is large, about 20%. Fig 1 is most useful in constraining rates. Chook et al JBC 271:48 pp 30472, 1996 say that the Kd is 0.2 uM for Shc binding to EGFR. The Kd for Grb direct binding is 0.7, so we'll ignore it.

    Sos.Grb2 acting as a Product in a reaction in  
    MAPK-bistability-fig1c 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
    Grb2_bind_Sos
  • MAPK-bistability
    -fig1c

    Accession No. : 35
  • Sos
    Pathway No. : 180
    0.025
    (uM^-1 s^-1)
    0.0168
    (s^-1)
    Kd(bf) = 0.672(uM)-Substrate
    Grb2
    Sos

    Product
    Sos.Grb2
    As there are 2 SH3 domains, this reaction could be 2nd order. I have a Kd of 22 uM from peptide binding (Lemmon et al JBC 269:50 pg 31653). However, Chook et al JBC 271:48 pg30472 say it is 0.4uM with purified proteins, so we believe them. They say it is 1:1 binding. Porfiri and McCormick JBC 271 also have related data. After comparing with the time-course of 1 min and the efficacy of activation of Ras, settle on Kd of 0.672 which is close to the Chook et al value.



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