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Molecule Parameter List for 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
Grb2 participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1000020

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.

    Grb2 acting as a Molecule in      MAPK-bistability-fig1c Network
    NameAccession NamePathway NameInitial Conc.
    (uM)    		Volume
    (fL)    		Buffered
    Grb2
  • MAPK-bistability
    -fig1c
    Accession No. : 35
    		• Sos
    Pathway No. : 180    		11000No
    There is probably a lot of it in the cell: it is also known as Ash (abundant src homology protein). Also Waters et al JBC 271:30 18224 1996 say that only a small fraction of cellular Grb is precipitated out when SoS is precipitated. As most of the Sos seems to be associated with Grb2, it would seem like there is a lot of the latter. Say 1 uM. This would comfortably saturate the 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
    1Grb2_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
      Same rates as Grb2_bind_Sos: Porfiri and McCormick JBC 271:10 pp 5871 1996 show that the binding is not affected by the phosphorylation.
    2Grb2_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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