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Molecule Parameter List for GDP-Ras

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

*GDP-Ras* 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	4	1	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.

GDP-Ras acting as a Molecule in Ajay_Bhalla_2004_PKM_MKP3_Tuning Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
GDP-Ras	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Ras Pathway No. : 333	0.5	1.5	No
GDP bound form. See Rosen et al Neuron 12 1207-1221 June 1994. the activation loop is based on Boguski and McCormick Nature 366 643-654 93 Assume Ras is present at about the same level as craf-1, 0.2 uM. Hallberg et al JBC 269:6 3913-3916 1994 estimate upto 5-10% of cellular Raf is assoc with Ras. Given that only 5-10% of Ras is GTP-bound, we need similar amounts of Ras as Raf.

GDP-Ras acting as a Substrate for 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
1	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
2	GEF* / GEF*-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 same as GEF-bg-act-ras
3	CaM-GEF / CaM-GEF-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 same as GEF-bg_act-ras
4	Shc*.Sos.Grb2 / Sos.Ras_GEF	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Shared_Object_ Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Pathway No. : 329	0.505051	0.02	4	explicit E-S complex	Substrate GDP-Ras Product GTP-Ras

GDP-Ras acting as a Product of 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
GAP / GAP-inact-ras	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Ras Pathway No. : 333	1.01039	10	4	explicit E-S complex	Substrate GTP-Ras Product GDP-Ras
From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) 5 Nov 2002: Changed ratio term to 4 from 100. Now we have k1=8.25e-5; k2=40, k3=10. k3 is still rate-limiting.

GDP-Ras 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
Ras-intrinsic-GT Pase	Ajay_Bhalla_ 2004_PKM_MKP3_ Tuning Accession No. : 77	Ras Pathway No. : 333	0.0001 (s^-1)	0 (s^-1)	-	-	Substrate GTP-Ras Product GDP-Ras
This is extremely slow (1e-4), but it is significant as so little GAP actually gets complexed with it that the total GTP turnover rises only by 2-3 X (see Gibbs et al, JBC 265(33) 20437-20422) and Eccleston et al JBC 268(36) 27012-27019 kf = 1e-4

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