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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
  • 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.

    Grb2 acting as a Molecule in  
    mkp1_feedback_effects Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    Grb2
  • mkp1_feedback_
    effects

    Accession No. : 4
  • Sos
    Pathway No. : 33
    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  
    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
    1Grb2_bind_Sos*
  • mkp1_feedback_
    effects

    Accession No. : 4
  • Sos
    Pathway No. : 33
    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
  • mkp1_feedback_
    effects

    Accession No. : 4
  • Sos
    Pathway No. : 33
    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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