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Reaction List for pathway Sos (Pathway Number 1107)

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 KfKbKdtauSubstrateProduct
1 dephosph_Sos0.001
(s^-1)		0
(s^-1)		--Sos_star
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
2 Grb2_bind_Sos0.025
(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.
3 Grb2_bind_Sos_
star		0.025
(uM^-1 s^-1)		0.0168
(s^-1)		Kd(bf) = 0.672(uM)-Sos_star
Grb2
Sos_star.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.
4 Shc_bind_
Sos.Grb2		0.5
(uM^-1 s^-1)		0.1
(s^-1)		Kd(bf) = 0.2(uM)-Sos.Grb2
Shc_star
  • Shc_
    star.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.
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