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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

Sos.Grb2 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	0	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.Grb2 acting as a Molecule in  Synaptic_Network Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
Sos.Grb2	Synaptic_ Network Accession No. : 16	Sos Pathway No. : 78	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  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
Shc_bind_ Sos.Grb2	Synaptic_ Network Accession No. : 16	Sos Pathway No. : 78	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  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.