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Reaction List for pathway Sos (Pathway Number 355) in Accession Ajay_Bhalla_2004_Feedback_Tuning (Accession Number 78)

Entries are grouped according to Pathway Number and they are alternately color coded using  and  color.
Further ordering can be done to the table header.  indicates that ordering is done according to ascending or descending order.
Keq is calculated only for first order reactions.
Kd is calculated only for second order reactions. [nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules]
  Reaction
Name
Pathway Name / 
Pathway No.
KfKbKdtauReagents
1 
  • Shc_bind_
    Sos.Grb2
  • Sos

    Pathway No. 355
    0.5
    (uM^-1 s^-1)
    0.1
    (s^-1)
    Kd(bf) = 0.2(uM)-  Substrate:
     Sos.Grb2
     SHC*

     Products:
     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.
    2 Grb2_bind_Sos*Sos

    Pathway No. 355
    0.025
    (uM^-1 s^-1)
    0.0168
    (s^-1)
    Kd(bf) = 0.672(uM)-  Substrate:
     Sos*
     Grb2

     Products:
     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 phosph.
    3 dephosph_SosSos

    Pathway No. 355
    0.001
    (s^-1)
    0
    (s^-1)
    --  Substrate:
     Sos*

     Products:
     Sos
      The only clue I have to these rates is from the time courses of the EGF activation, which is around 1 to 5 min. The dephosph would be expected to be of the same order, perhaps a bit longer. Lets use 0.002 which is about 8 min. Sep 17: The transient activation curve matches better with kf = 0.001
    4 Grb2_bind_SosSos

    Pathway No. 355
    0.025
    (uM^-1 s^-1)
    0.0168
    (s^-1)
    Kd(bf) = 0.672(uM)-  Substrate:
     Grb2
     Sos

     Products:
     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.

     
    Result: 1 - 4 of 4 rows are displayed



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