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Molecule Parameter List for MKP-1

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

MKP-1 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	2	1	1	1	2

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
MAPK_MKP1_ oscillation	9	Network	Shared_Object_MAPK_MKP1_oscillation,  PKC,  MAPK,   PLA2,  Ras
This model relates to figure 5 in Bhalla US, Iyengar R. Chaos (2001) 11(1):221-226. It includes the model used for figures 2-4 and also has MKP-1 induction by MAPK activity in the synapse. PP2A is set to 0.16 uM and MKP synthesis is varied from 5x to 40 x basal to get a range of interesting behaviours.

MKP-1 acting as a Molecule in  MAPK_MKP1_oscillation Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
MKP-1	MAPK_MKP1_ oscillation Accession No. : 9	Shared_Object_ MAPK_MKP1_ oscillation Pathway No. : 59	0.0027	1000	No
MKP-1 deph and inact MAPK in vivo: Sun et al Cell 75 487-493 1993. Kinetics from Charles et al PNAS 90:5292-5296 1993. They cite Charles et al Oncogene 7 187-190 for half-life of MKP1/3CH is 40 min. 80% deph of MAPK in 20 min Sep 17 1997: CoInit now 0.4x to 0.0032. See parm searches from jun96 on. 30 May 2k: CoInit now 0.0027, but not so critical as its prdn is regulated.

MKP-1 acting as an Enzyme in  MAPK_MKP1_oscillation Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	MKP-1 / MKP1-tyr-deph	MAPK_MKP1_ oscillation Accession No. : 9	Shared_Object_ MAPK_MKP1_ oscillation Pathway No. : 59	0.0666667	1	4	Classical Michaelis-Menten V = Etot.S.Kcat/Km+S	Substrate MAPK-tyr Product MAPK
	The original kinetics have been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. As noted in the NOTES, the only constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. It would be nice to have more accurate estimates of rate consts and MKP-1 levels from the literature. Effective Km : 67 nM kcat = 1.43 umol/min/mg
2	MKP-1 / MKP1-thr-deph	MAPK_MKP1_ oscillation Accession No. : 9	Shared_Object_ MAPK_MKP1_ oscillation Pathway No. : 59	0.0666667	1	4	Classical Michaelis-Menten V = Etot.S.Kcat/Km+S	Substrate MAPK* Product MAPK-tyr
	See MKP1-tyr-deph

MKP-1 acting as a Substrate for an Enzyme in  MAPK_MKP1_oscillation Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
MAPK*  / MKP-1-phosph	MAPK_MKP1_ oscillation Accession No. : 9	Shared_Object_ MAPK_MKP1_ oscillation Pathway No. : 59	25.641	1	4	explicit E-S complex	Substrate MKP-1 Product MKP-1-ser359*
3 Feb 2000. See Brondello et al Science 286:2514 1999. Rates assumed standard MAPK rates based on Sanghera et al JBC 265(1):53-57 1990. 24 Apr 2K, based on 12 Feb 2K: scaled by 0.1 to 3.25e-7,4,1

MKP-1 acting as a Product of an Enzyme in  MAPK_MKP1_oscillation Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
nuc_MAPK*  / MKP-1-synthesis	MAPK_MKP1_ oscillation Accession No. : 9	MAPK Pathway No. : 61	27.3632	0.0001	10	explicit E-S complex	Substrate MKP-1-gene Product MKP-1
5 Feb 2000 This is a crude model of activation of MKP1 production by MAPK. Time-course poorly constrained: 10 min to > 100 min. Rates are further constrained by the known degradation rates of MKP-1, also in this model. Peak MKP-1 is about 10 times basal (from Brondello et al Science 286:2514 1999). Max MAPK ~.25 uM, degradation 45 min. So this enz has to provide 22nM MKP every 45 min.

MKP-1 acting as a Substrate in a reaction in  MAPK_MKP1_oscillation 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
turnover_MKP1	MAPK_MKP1_ oscillation Accession No. : 9	MAPK Pathway No. : 61	0.0004 (s^-1)	0 (s^-1)	-	-	Substrate MKP-1 Product Ubiquitination
3 Feb 2000. Rate of turnover of non-phosph form of MKP1 is from Brondello et al Science 286:2514 1999. Tau is about 45 min.

MKP-1 acting as a Product in a reaction in  MAPK_MKP1_oscillation 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	MKP-1-basal-synt h	MAPK_MKP1_ oscillation Accession No. : 9	MAPK Pathway No. : 61	0 (s^-1)	0 (s^-1)	-	-	Substrate MKP-1-gene Product MKP-1
	3 Feb 2000. The levels of basal MAPK are so low that we need to have a basal mechanism for making MKP-1. This is easy, as the degradation tau is 45 min and basal MKP-1 levels are 2.4 nM in our model. x * 1 uM = 2.4e-3 * 0.37e-3 = 8.9e-7 May 30 2k. Basal levels shifted up a bit. kf now 1.0e-6 Jun 3 2k: kf now 8e-7 Jun 4 2k: kf = 7e-7
2	MKP-1*dephosph	MAPK_MKP1_ oscillation Accession No. : 9	MAPK Pathway No. : 61	0.01 (s^-1)	0 (s^-1)	-	-	Substrate MKP-1-ser359* Product MKP-1
	24 Apr 2K: Based on 12 Feb 2K: Scaled up 10x so kf=0.01, kb=0