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Molecule Parameter List for Sos | 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 acting as a Molecule in mkp1_feedback_effects Network
Name | Accession Name | Pathway Name | Initial Conc. (uM) | Volume (fL) | Buffered | Sos | mkp1_feedback_ effects Accession No. : 4 | Sos Pathway No. : 33 | 0.1 | 1000 | No | I have tried using low (0.02 uM) initial concs, but these give a very flat response to EGF stim although the overall activation of Ras is not too bad. I am reverting to 0.1 because we expect a sharp initial response, followed by a decline. |
Sos 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 | 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. |
Sos 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 | dephosph_Sos | mkp1_feedback_ effects Accession No. : 4 | Sos Pathway No. : 33 | 0.001 (s^-1) | 0 (s^-1) | - | - | Substrate Sos*
Product 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 |
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