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Molecule Parameter List for craf-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

craf-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	0	1	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.

craf-1 acting as a Molecule in  mkp1_feedback_effects Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
craf-1	mkp1_feedback_ effects Accession No. : 4	MAPK Pathway No. : 35	0.2	1000	No
Strom et al 1990 Oncogene 5 pp 345-51 report high general expression in all tissues. Huang and Ferrell 1996 PNAS 93(19):10078 use a value of 3 nM for oocytes. Here we stick with a much higher expression based on the Strom report.

craf-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
PKC-active  / PKC-act-raf	mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	66.6667	4	4	explicit E-S complex	Substrate craf-1 Product craf-1*
Rate constants are from Chen SJ, Klann E, Gower MC, Powell CM, Sessoms JS, Sweatt JD. (1993) Biochemistry 32(4):1032-1039. k3 = 4 Km for this substrate is trickier. Specific substrates are in the uM range, so we use a higher Km here. This may be too conservative in which case PKC would have a still higher effect on raf. The presence of this phosphorylation and activation step is from Kolch W, Heidecker G, Kochs G, Hummel R, Vahidi H, Mischak H, Finkenzeller G, Marme D, Rapp UR. (1993) Nature 364(6434):249-52.

craf-1 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
PPhosphatase2A  / craf-deph	mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	15.6566	6	4.16667	explicit E-S complex	Substrate craf-1* Product craf-1
See parent PPhosphatase2A for parms

craf-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
Ras-act-unphosph -raf	mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	6 (uM^-1 s^-1)	1 (s^-1)	Kd(bf) = 0.1667(uM)	-	Substrate GTP-Ras craf-1 Product RGR
Based on rates of Ras-act-craf which has Kf=60, Kb= 0.5. This reaction was introduced to account for the PKC-independent activation of MAPK. This reac should have less affinity but similar tau as compared to the Ras-cat-craf, since the phosphorylated Raf form has a greater effect on MAPK.