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Molecule Parameter List for GAP

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

GAP 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	1	1	0	0	1

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.

GAP acting as a Molecule in  mkp1_feedback_effects Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
GAP	mkp1_feedback_ effects Accession No. : 4	Ras Pathway No. : 37	0.002	1000	No
GTPase-activating proteins. See Boguski and McCormick 1993 Nature 366:643-654 Turn off Ras by helping to hydrolyze bound GTP. This one is probably NF1, ie., Neurofibromin as it is inhibited by AA and lipids, and expressed in neural cells. p120-GAP is also a possible candidate, but is less regulated. Both may exist at similar levels. See Eccleston et al JBC 268(36) pp27012-19 Level=.002

GAP 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
GAP / GAP-inact-ras	mkp1_feedback_ effects Accession No. : 4	Ras Pathway No. : 37	1.0104	10	100	explicit E-S complex	Substrate GTP-Ras Product GDP-Ras
From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). The two sets of values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) This is one of the rare cases where we have direct info on the k3 being rate-limiting. Hence the ratio I use for the k2:k3 rates is 100 rather than the usual 4.

GAP 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-inact-GAP	mkp1_feedback_ effects Accession No. : 4	Shared_Object_ mkp1_feedback_ effects Pathway No. : 32	66.6667	25	4	explicit E-S complex	Substrate GAP Product GAP*
Rate constants are generic PKC rates. This reaction inactivates GAP. The reaction is from Boguski MS and McCormick F (1993) Nature 366(6456):643-54. The phosphorylation Vmax is 6x higher to account for balance of GDP-Ras:GDP-Ras.

GAP 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
dephosph-GAP	mkp1_feedback_ effects Accession No. : 4	Ras Pathway No. : 37	0.1 (s^-1)	0 (s^-1)	-	-	Substrate GAP* Product GAP
Assume a reasonably good rate for dephosphorylating it, 0.1/sec. This fits well with resting levels of active kinase and the degree of activation as well as time-course of turnoff of Ras activation, but data is quite indirect.