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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	1	2	1	0	1	2

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.

MKP-1 acting as a Molecule in  mkp1_feedback_effects Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
MKP-1	mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	0.0004	1000	No
MKP-1 dephosphorylates and inactivates MAPK in vivo: Sun H, Charles CH, Lau LF, Tonks NK. (1993) Cell 75(3):487-493. See Charles CH, Sun H, Lau LF, Tonks NK. (1993) Proc Natl Acad Sci U S A. 90(11):5292-5296 and Charles CH, Abler AS, Lau LF. (1992) Oncogene 7(1):187-190 for half-life of MKP1/3CH is 40 min. 80% deph of MAPK in 20 min The protein is 40 KDa. 22 Apr 2001: CoInit =0.4nM but this is really an emergent property of the rate of induction of the phosphatase at steady-state in balance with the degradation rate.

MKP-1 acting as a Summed Molecule in  mkp1_feedback_effects Network

Accession Name	Pathway Name	Target	Input
mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	tot_MKP1	MKP-1 MKP-1-ser359* MKP-1**
Total available active MKP-1. This sums the levels of the non-phosphorylated, singly phosphorylated and doubly phosphorylated forms. It is used primarily for graphing the total MKP-1 level.

MKP-1 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
1	MKP-1 / MKP1-tyr-deph	mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	0.0666667	1	4	Classical Michaelis-Menten V = Etot.S.Kcat/Km+S	Substrate MAPK-tyr Product MAPK
	The original kinetics from Bhalla US and Iyengar R. (1999) Science 283(5400):381-387 have now been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. The main constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. See Charles CH, Sun H, Lau LF, Tonks NK. (1993) Proc Natl Acad Sci U S A. 90(11):5292-5296 and Charles CH, Abler AS, Lau LF. (1992) Oncogene 7(1):187-190. Effective Km : 67 nM kcat = 1.43 umol/min/mg.
2	MKP-1 / MKP1-thr-deph	mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	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  mkp1_feedback_effects Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
MAPK*  / MKP-1-phosph	mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	25.641	1	4	explicit E-S complex	Substrate MKP-1 Product MKP-1-ser359*
3 Feb 2000. MAPK rates based on Sanghera JS, Paddon HB, Bader SA, Pelech SL. (1990) 265(1):52-57. The Vmax is scaled down 10 fold to match the time-course of phosph by MAPK, from Brondello JM, Pouyssegur J, McKenzie FR. (1999) Science 286(5449):2514-2517.

MKP-1 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
turnover_MKP1	mkp1_feedback_ effects Accession No. : 4	MAPK Pathway No. : 35	0.0004 (s^-1)	0 (s^-1)	-	-	Substrate MKP-1 Product Ubiquitination
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  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
1	MKP-1*dephosph	mkp1_feedback_ effects Accession No. : 4	MAPK Pathway No. : 35	0.0001 (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 13 Apr 2001: MKP1* Goes down too fast, equil amount too small. Note that tau for turnover is 150 min. Doesn't make sense to have this tau be so much less. Go for 1e-4
2	MKP1_synth	mkp1_feedback_ effects Accession No. : 4	MAPK Pathway No. : 35	0.002 (s^-1)	0 (s^-1)	Not applicable**	-	Substrate MKP1-RNA Product MKP-1
	This is a 'black box' approximation to the process of translation. I assume that there is unity stoichiometry, that is, a single RNA gives a single protein. This is obviously wrong, but since the RNA level itself is just a ratio against baseline, the conversion factor is absorbed there.

** This is a trasport reation between compartments of different volumes. Therefore Kd is not applicable. Please Note Kf, Kb units are in number of molecules instead of concentration