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Reaction List for pathway Sos (Pathway Number 78) | | 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 reactions is not considered. |
| | Name | Kf | Kb | Kd | tau | Substrate | Product | | 1 |
dephosph_Sos | 0.001
(s^-1) | 0
(s^-1) | - | - | Sos*
| Sos
| | | The best 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 | | 2 |
Grb2_bind_Sos | 0.025
(uM^-1 s^-1) | 0.0168
(s^-1) | Kd(bf) = 0.672(uM) | - | Grb2
Sos
| 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. | | 3 |
Grb2_bind_Sos* | 0.025
(uM^-1 s^-1) | 0.0168
(s^-1) | Kd(bf) = 0.672(uM) | - | Sos*
Grb2
| 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. | | 4 |
Shc_bind_
Sos.Grb2 | 0.5
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.2(uM) | - | Sos.Grb2
SHC*
| 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. |
Pathway Details Molecule List Enzyme List Reaction List
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