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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

Sos participated as	Molecule	Sum total of	Enzyme	Substrate of an enzyme	Product of an enzyme	Substrate in Reaction	Product in Reaction
No. of occurrences	1	0	0	1	0	1	1

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
Synaptic_ Network	16	Network	Shared_Object_Synaptic_Network,  PKC,  PLA2,   PLCbeta,  Gq,  MAPK,   Ras,  EGFR,  Sos,   PLC_g,  CaMKII,  CaM,   PP1,  PP2B,  PKA,   AC,  CaRegulation
This model is an annotated version of the synaptic signaling network. The primary reference is Bhalla US and Iyengar R. Science (1999) 283(5400):381-7 but several of the model pathways have been updated. Bhalla US Biophys J. 2002 Aug;83(2):740-52 Bhalla US J Comput Neurosci. 2002 Jul-Aug;13(1):49-62

Sos acting as a Molecule in  Synaptic_Network Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
Sos	Synaptic_ Network Accession No. : 16	Sos Pathway No. : 78	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 for an Enzyme in  Synaptic_Network Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
MAPK*  / phosph_Sos	Synaptic_ Network Accession No. : 16	Shared_Object_ Synaptic_ Network Pathway No. : 70	2.5641	10	4	explicit E-S complex	Substrate Sos Product Sos*
See Porfiri and McCormick JBC 271:10 pp5871 1996 for the existence of this step. We'll take the rates from the ones used for the phosph of Raf by MAPK. Sep 17 1997: The transient activation curve matches better with k1 up by 10 x.

Sos acting as a Substrate in a reaction in  Synaptic_Network 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	Synaptic_ Network Accession No. : 16	Sos Pathway No. : 78	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  Synaptic_Network 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	Synaptic_ Network Accession No. : 16	Sos Pathway No. : 78	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