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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	1	1	0	0

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

MAPKK acting as a Molecule in  Synaptic_Network Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
MAPKK	Synaptic_ Network Accession No. : 16	MAPK Pathway No. : 75	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 Initial concentration is 0.18

MAPKK 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
Raf-GTP-Ras*  / Raf-GTP-Ras*.1	Synaptic_ Network Accession No. : 16	MAPK Pathway No. : 75	0.159091	0.105	4	explicit E-S complex	Substrate MAPKK Product MAPKK-ser
This enzyme activity refers to the complex of phosphorylated Raf and activated Ras. Starting point for 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 who report a Km of 0.8 uM and Vmax of ~500 fm/min/ug for MAPKK. These parms cannot reach the observed 4X stim of MAPK. So we increase the affinity, ie, raise k1 5X to 5.5e-6 which is equivalent to a 5x reduction in Km to about 0.16.

MAPKK acting as a Product of an Enzyme in  Synaptic_Network Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
PPhosphatase2A  / MAPKK-deph-ser	Synaptic_ Network Accession No. : 16	Shared_Object_ Synaptic_ Network Pathway No. : 70	15.6566	6	4.16667	explicit E-S complex	Substrate MAPKK-ser Product MAPKK
See parent PPhostphatase2A description for rate details