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Molecule Parameter List for MAPKK

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

*MAPKK* 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	4	1	0	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
mRNA synthesis	94	Network	kinetics, compartment_1, compartment_2
The model consists of three major pathways: Calcium-calmodulin dependent protein kinase IV (CaMKIV), Mitogen-activated protein kinase (MAPK) and Protein Phosphatase 1 (PP1). Each of these converged on CREB activation. We also modeled further interactions with Transducer of regulated CREB activity 1 (TORC1) and the protein kinase A (PKA) pathway.

MAPKK acting as a Molecule in mRNA synthesis Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
MAPKK	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	0.18	1000	No
Conc is from Seger et al JBC 267:20 pp14373 (1992) mwt is 45/46 Kd We assume that phosphorylation on both ser and thr is needed for activiation. See Kyriakis et al Nature 358 417 1992 Init conc of total is 0.18 Ortiz et al 1995 J Neurosci 15(2):1285-1297 suggest that levels are higher in hippocampus than other brain regions, and further elevated in synapses. Estimate 3x higher levels than before, at 0.5 uM. Similar results from Schipper et al 1999 Neuroscience 93(2):585-595 but again lacking in quantitation.

MAPKK acting as a Substrate for an Enzyme in mRNA synthesis Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	bRaf_Rap1GTP / braf_dash_rap1_ dash_GTP1	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	0.16	0.3	4	explicit E-S complex	Substrate MAPKK Product MAPKK_dash_ser

2	Raf_dash_GTP_ dash_Ras / Raf_dash_GTP_ dash_Ras.1	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	0.1591	0.3	4	explicit E-S complex	Substrate MAPKK Product MAPKK_dash_ser
	Kinetics are the same as for the craf_1* activity, ie., k1=5.5e-6, k2=0.42, k3 = 0.105 These are basedo n Force et al PNAS USA 91 1270-1274, 1994., but k1 is scaled up 5x (ie., Km is scaled down 5x to the value used here and for craf_1* activity: Km = 0.1591).
3	braf_dash_GTP_ dash_Ras / braf_dash_GTP_ dash_Ras1	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	0.16	0.2	4	explicit E-S complex	Substrate MAPKK Product MAPKK_dash_ser

4	Raf_star_dash_ GTP_dash_Ras / Raf_star_dash_ GTP_dash_Ras.1	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	0.1591	0.3	4	explicit E-S complex	Substrate MAPKK Product MAPKK_dash_ser
	Kinetics are the same as for the craf-1* activity, ie., k1=1.1e-6, k2=.42, k3 =0.105 These are based on Force et al PNAS USA 91 1270-1274 1994. These parms cannot reach the observed 4X stim of MAPK. So lets increase the affinity, ie, raise k1 10X to 1.1e-5 Lets take it back down to where it was. Back up to 5X: 5.5e-6

MAPKK acting as a Product of an Enzyme in mRNA synthesis Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
PPhosphatase2A / MAPKK_dash_ deph_dash_ser	mRNA synthesis Accession No. : 94	kinetics Pathway No. : 1112	15.6568	6	4	explicit E-S complex	Substrate MAPKK_dash_ser Product MAPKK

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