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Molecule Parameter List for Raf*-GTP-Ras | 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 |
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. |
Raf*-GTP-Ras acting as a Molecule in mkp1_feedback_effects Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | Raf*-GTP-Ras | mkp1_feedback_
effects
Accession No. : 4 | MAPK
Pathway No. : 35 | 0 | 1000 | No | | This is the main activated form of craf. It requires binding to ras for activation, but the presence of the phosphorylation increases this binding. See Leevers 1994 Nature 369:411-414 and Hallberg et al 1994 JBC 269(6):3913-3916 |
Raf*-GTP-Ras 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 | Raf*-GTP-Ras /
Raf*-GTP-Ras.1
| mkp1_feedback_
effects
Accession No. : 4 | MAPK
Pathway No. : 35 | 0.159091 | 0.105 | 4 | explicit E-S complex | Substrate
MAPKK
Product
MAPKK-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. They report Km for MAPKK of 0.8 uM. and a Vmax of ~500 fm/min/ug. These parms cannot reach the observed 4X stimulation of MAPK. So we increase the affinity, ie, raise k1 5x to 5.5e-6 which is equivalent to 5-fold reduction in Km to about 0.16. This is, of course, dependent on the amount of MAPKK present. | | 2 | Raf*-GTP-Ras /
Raf*-GTP-Ras.2
| mkp1_feedback_
effects
Accession No. : 4 | MAPK
Pathway No. : 35 | 0.159091 | 0.105 | 4 | explicit E-S complex | Substrate
MAPKK-ser
Product
MAPKK*
| | | Same kinetics as other c-raf activated forms. See Force et al PNAS 91 1270-1274 1994. |
Raf*-GTP-Ras 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 | | Ras-act-craf | mkp1_feedback_
effects
Accession No. : 4 | Shared_Object_
mkp1_feedback_
effects
Pathway No. : 32 | 60
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.0083(uM) | - | Substrate
GTP-Ras
craf-1*
Product
Raf*-GTP-Ras
| | Assume binding is fast and limited only by available Ras*. So kf = kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to about 1e-4, giving a Kf of 60 for Kb of 0.5 and a tau of approx 2 sec. Based on: Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414. Also see Koide et al 1993 PNAS USA 90(18):8683-8686 |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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