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Molecule Parameter List for 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

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	1	0	1	1	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
mkp1_feedback_ effects	4	Network	Shared_Object_mkp1_feedback_effects, Sos, PKC, MAPK, PLA2, Ras, PDGFR
This is a network involving the MAPK-PKC feedback loop with input from the PDGFR in the synapse. The distinctive feature of this model is that it includes MKP-1 induction by MAPK, and the consequent inhibitory regulation of MAPK and the feedback loop. Lots of interesting dynamics arise from this. This link provides supplementary material for the paper Bhalla US et al. Science (2002) 297(5583):1018-23. In the form of several example simulations and demos for the figures in the paper.

GEF* acting as a Molecule in mkp1_feedback_effects Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
GEF*	mkp1_feedback_ effects Accession No. : 4	Ras Pathway No. : 37	0	1000	No
Phosphorylated and thereby activated form of GEF. See, e.g. Orita et al JBC 268:34 25542-25546 1993, Gulbins et al. It is not clear whether there is major specificity for tyr or ser/thr.

GEF* acting as an Enzyme in mkp1_feedback_effects Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
GEF* / GEF*-act-ras	mkp1_feedback_ effects Accession No. : 4	Ras Pathway No. : 37	0.505051	0.02	4	explicit E-S complex	Substrate GDP-Ras Product GTP-Ras
Kinetics from Orita et al JBC 268(34):25542-25546. Note that the Vmax is slow, but it does match the slow GTP hydrolysis rates.

GEF* acting as a Product of an Enzyme in mkp1_feedback_effects Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
PKC-active / PKC-act-GEF	mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	66.6667	4	4	explicit E-S complex	Substrate inact-GEF Product GEF*
Rate constants are generic PKC rates. See Chen SJ, Klann E, Gower MC, Powell CM, Sessoms JS, Sweatt JD. (1993) Biochemistry 32(4):1032-9. 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.

GEF* acting as a Substrate in a reaction in mkp1_feedback_effects 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-GEF	mkp1_feedback_ effects Accession No. : 4	Ras Pathway No. : 37	0.1 (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

Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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