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Reaction List for pathway Sos (Pathway Number 78) in Accession Synaptic_Network (Accession Number 16) | 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] |
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Reaction Name | Pathway Name / Pathway No. | Kf | Kb | Kd | tau | Reagents | 1 | Shc_bind_ Sos.Grb2 | Sos
Pathway No. 78 | 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. 78 | 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 phosphorylation. | 3 | dephosph_Sos | Sos
Pathway No. 78 | 0.001 (s^-1) | 0 (s^-1) | - | - | Substrate: Sos*
Products: 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 | 4 | Grb2_bind_Sos | Sos
Pathway No. 78 | 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. 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. |
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