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Molecule Parameter List for GEF-Gprot-bg

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

GEF-Gprot-bg 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	1	0	0	0	1

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning	77	Network	Shared_Object_Ajay_Bhalla_2004_PKM_MKP3_Tuning,  PKC,  PLA2,   PLCbeta,  Ras,  Gq,   MAPK,  EGFR,  Sos,   PLC_g,  CaMKII,  CaM,   PP1,  PP2B,  PKA,   AC,  MKP3,  PKM
This model is based on Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80. This is the feedforward model with MPK3 from figure 8a.

GEF-Gprot-bg acting as a Molecule in  Ajay_Bhalla_2004_PKM_MKP3_Tuning Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
GEF-Gprot-bg	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Ras Pathway No. : 333	0	1.5	No
Guanine nucleotide exchange factor. This activates raf by exchanging bound GDP with GTP. I have left the GDP/GTP out of this reaction, it would be trivial to put them in. See Boguski & McCormick. Possible candidate molecules: RasGRF, smgGDS, Vav (in dispute). rasGRF: Kcat= 1.2/min Km = 680 nM smgGDS: Kcat: 0.37 /min, Km = 220 nM. vav: Turnover up over baseline by 10X,

GEF-Gprot-bg acting as an Enzyme in  Ajay_Bhalla_2004_PKM_MKP3_Tuning Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
GEF-Gprot-bg / GEF-bg_act-ras	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Ras Pathway No. : 333	0.505051	0.02	4	explicit E-S complex	Substrate GDP-Ras Product GTP-Ras
Kinetics based on the activation of Gq by the receptor complex in the Gq model (in turn based on the Mahama and Linderman model) k1 = 2e-5, k2 = 1e-10, k3 = 10 (I do not know why they even bother with k2). Lets put k1 at 2e-6 to get a reasonable equilibrium More specific values from, eg.g: Orita et al JBC 268(34) 25542-25546 from rasGRF and smgGDS: k1=3.3e-7; k2 = 0.08, k3 = 0.02

GEF-Gprot-bg acting as a Product in a reaction in  Ajay_Bhalla_2004_PKM_MKP3_Tuning 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
bg-act-GEF	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Ras Pathway No. : 333	6 (uM^-1 s^-1)	1 (s^-1)	Kd(bf) = 0.1667(uM)	-	Substrate BetaGamma inact-GEF Product GEF-Gprot-bg
SoS/GEF is present at 50 nM ie 3e4/cell. BetaGamma maxes out at 9e4. Assume we have 1/3 of the GEF active when the BetaGamma is 1.5e4. so 1e4 * kb = 2e4 * 1.5e4 * kf, so kf/kb = 3e-5. The rate of this equil should be reasonably fast, say 1/sec