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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 | 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 |
Raf-GTP-Ras* acting as a Molecule in Synaptic_Network Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | Raf-GTP-Ras* | Synaptic_
Network
Accession No. : 16 | MAPK
Pathway No. : 75 | 0 | 1000 | No | | This is the main activated form of craf. It really refers to the complex of GTP-Ras with phosphorylated Raf. See Leevers 1994 Nature 369:411-414 and Hallberg et al 1994 JBC 269(6):3913-3916. The naming is a bit awkward but kept in this model for consistency with previous models (Bhalla and Iyengar 1999 Science 283:381-387) |
Raf-GTP-Ras* acting as an Enzyme in Synaptic_Network 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
| 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. | | 2 | Raf-GTP-Ras* /
Raf-GTP-Ras*.2
| Synaptic_
Network
Accession No. : 16 | MAPK
Pathway No. : 75 | 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 Synaptic_Network 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 | Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 24
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.0208(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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