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Molecule Parameter List for inact-GEF

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

inact-GEF 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	2	0	2	2

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

inact-GEF acting as a Molecule in  Synaptic_Network Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
inact-GEF	Synaptic_ Network Accession No. : 16	Ras Pathway No. : 76	0.1	1000	No
This is the amount of inactive GEF available to the system. The value is the same as the estimated amount of SoS, though I treat it here as a different pool. Probably several molecules can function as GEFs and this is a simplification. Orita et al JBC 268(34):25542-25546 Gulbins et al 1994 Mol Cell Biol 14(2):906-913

inact-GEF acting as a Substrate for an Enzyme in  Synaptic_Network Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	PKC-active  / PKC-act-GEF	Synaptic_ Network Accession No. : 16	Shared_Object_ Synaptic_ Network Pathway No. : 70	3.33333	4	4	explicit E-S complex	Substrate inact-GEF Product GEF*
	Rate constants are generic PKC rates. See Chen et al 1993 Biochem 32:1032 This reaction activates GEF. Gives >= 2X stim of ras, and a 2X stim of MAPK over amount from direct phosph of c-raf. Note that it is a push-pull reaction, and also get effect through phosph and inact of GAPs.
2	PKA-active  / PKA-phosph-GEF	Synaptic_ Network Accession No. : 16	Shared_Object_ Synaptic_ Network Pathway No. : 70	7.5	9	4	explicit E-S complex	Substrate inact-GEF Product inact-GEF*
	This pathway inhibits Ras when cAMP is elevated. See: Hordijk et al JBC 269:5 3534-3538 1994 Burgering et al EMBO J 12:11 4211-4220 1993 The rates are the same as used in PKA-phosph-I1

inact-GEF 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
1	bg-act-GEF	Synaptic_ Network Accession No. : 16	Ras Pathway No. : 76	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
2	CaM-bind-GEF	Synaptic_ Network Accession No. : 16	Ras Pathway No. : 76	60 (uM^-1 s^-1)	1 (s^-1)	Kd(bf) = 0.0167(uM)	-	Substrate CaM-Ca4 inact-GEF Product CaM-GEF
	We have no numbers for this. It is probably between the two extremes represented by the CaMKII phosph states, and I have used guesses based on this. kf=1e-4 kb=1 The reaction is based on Farnsworth et al Nature 376 524-527 1995

inact-GEF 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
1	dephosph-GEF	Synaptic_ Network Accession No. : 16	Ras Pathway No. : 76	1 (s^-1)	0 (s^-1)	-	-	Substrate GEF* Product inact-GEF
	This rate is based on the known ratio of GDP-Ras to GTP-Ras. Basal: Ras.GTP = 7% Stimulated 15% Time course is within 10 min, probably much faster as not all early data points are there. See Gibbs et al JBC 265(33):20437-20422
2	dephosph-inact-G EF*	Synaptic_ Network Accession No. : 16	Ras Pathway No. : 76	1 (s^-1)	0 (s^-1)	-	-	Substrate inact-GEF* Product inact-GEF