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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
mTOR_pathway	92	Network	Shared_Object_mTOR_pathway,  AKT_mod,  S6Kinase,   PI3K_mod,  TrKB_mod,  mTOR_model,   MAPK,  PKC,  4E-BP_mod,   Ras,  Sos,  43S_complex,   CaM
This model consists of various sub-modules. They are as follows: 1) BDNF receptor signaling 2) AKT signaling 3) 4E-BP model 4) S6 Kinase model 5) CaMKIII model 6) Protein synthesis model 7) CaM 8) PKC 9) MAPK model.

Sos acting as a Molecule in  mTOR_pathway Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
Sos	mTOR_pathway Accession No. : 92	Sos Pathway No. : 1107	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. Sep 17 1997: The transient activation curve looks better with [Sos] = 0.05. Apr 26 1998: Some error there, it is better where it was at 0.1

Sos acting as a Substrate for an Enzyme in  mTOR_pathway Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
MAPK_star  / phosph_Sos	mTOR_pathway Accession No. : 92	Shared_Object_ mTOR_pathway Pathway No. : 1097	2.5641	10	4	explicit E-S complex	Substrate Sos Product Sos_star
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  mTOR_pathway 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	mTOR_pathway Accession No. : 92	Sos Pathway No. : 1107	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.

Sos acting as a Product in a reaction in  mTOR_pathway 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	mTOR_pathway Accession No. : 92	Sos Pathway No. : 1107	0.001 (s^-1)	0 (s^-1)	-	-	Substrate Sos_star Product 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