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Molecule Parameter List for GTP-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

*GTP-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	1	4	2	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
EGFR_MAPK	58	Network	Shared_Object_EGFR_MAPK, MAPK, Ras, EGFR, Sos
Model of MAPK activation by EGFR in the synapse. Demonstration programs using this model are available here. Primary citation:Bhalla US. Biophys J. (2004) 87(2):745-53.

GTP-Ras acting as a Molecule in EGFR_MAPK Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
GTP-Ras	EGFR_MAPK Accession No. : 58	Ras Pathway No. : 231	0	1000	No
Only a very small fraction (7% unstim, 15% stim) of ras is GTP-bound. Gibbs et al JBC 265(33) 20437

GTP-Ras acting as a Substrate for an Enzyme in EGFR_MAPK Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
GAP / GAP-inact-ras	EGFR_MAPK Accession No. : 58	Ras Pathway No. : 231	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.

GTP-Ras acting as a Product of an Enzyme in EGFR_MAPK 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	EGFR_MAPK Accession No. : 58	Ras Pathway No. : 231	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	EGFR_MAPK Accession No. : 58	Ras Pathway No. : 231	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	EGFR_MAPK Accession No. : 58	Ras Pathway No. : 231	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	EGFR_MAPK Accession No. : 58	Shared_Object_ EGFR_MAPK Pathway No. : 229	0.505051	0.02	4	explicit E-S complex	Substrate GDP-Ras Product GTP-Ras

GTP-Ras acting as a Substrate in a reaction in EGFR_MAPK 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
1	Ras-act-craf	EGFR_MAPK Accession No. : 58	Shared_Object_ EGFR_MAPK Pathway No. : 229	24 (uM^-1 s^-1)	0.5 (s^-1)	Kd(bf) = 0.0208(uM)	-	Substrate GTP-Ras craf-1* Product Raf-GTP-Ras*
	Assume the binding is fast and limited only by the amount of Ras* available. So kf=kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 (I don't....
2	Ras-intrinsic-GT Pase	EGFR_MAPK Accession No. : 58	Ras Pathway No. : 231	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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