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Molecule Parameter List for Sos.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 |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | mkp1_feedback_
effects | 4 | Network |
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. |
Sos.Grb2 acting as a Molecule in mkp1_feedback_effects Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | Sos.Grb2 | mkp1_feedback_
effects
Accession No. : 4 | Sos
Pathway No. : 33 | 0 | 1000 | No | | For simplicity I treat the activation of Sos as involving a single complex comprising Sos, Grb2 and Shc*. This is reasonably documented: Sasaoka et al 1994 JBC 269(51):32621-5 Chook et al JBC 1996 271(48):30472 |
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. |
| Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | Shc_bind_
Sos.Grb2 | mkp1_feedback_
effects
Accession No. : 4 | Sos
Pathway No. : 33 | 0.5
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.2(uM) | - | Substrate
SHC*
Sos.Grb2
Product
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. |
Sos.Grb2 acting as a Product 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. |
| Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | Grb2_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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