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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 | Ajay_Bhalla_
2007_Bistable | 79 | Network |
Shared_Object_Ajay_Bhalla_2007_Bistable, PKC, PLA2,
MAPK, Ras, CaM | This is a model of ERKII signaling which is bistable due to feedback. The feedback occurs through ERKII phosphorylation of phospholipase A2 (PLA2), leading to increased production of arachidonic acid (AA), which activates protein kinase C (PKC) which activates c-Raf which is upstream of ERKII.
The model is a highly simplified variant of more detailed bistable models of MAPK signaling (Bhalla US, Iyengar R. Science. 1999 Jan 15;283(5400):381-7, Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80) |
Raf*-GTP-Ras acting as a Molecule in Ajay_Bhalla_2007_Bistable Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | Raf*-GTP-Ras | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | MAPK
Pathway No. : 366 | 0 | 125.7 | No |
Raf*-GTP-Ras acting as an Enzyme in Ajay_Bhalla_2007_Bistable 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
| Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | MAPK
Pathway No. : 366 | 0.159096 | 0.3 | 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. These parms cannot reach the observed 4X stim of MAPK. So lets increase the affinity, ie, raise k1 10X to 1.1e-5 Lets take it back down to where it was. Back up to 5X: 5.5e-6 | | 2 | Raf*-GTP-Ras /
Raf*-GTP-Ras.2
| Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | MAPK
Pathway No. : 366 | 0.159096 | 0.3 | 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. k1 = 1.1e-6, k2 = .42, k3 = 1.05 raise k1 to 5.5e-6 |
Raf*-GTP-Ras acting as a Product in a reaction in Ajay_Bhalla_2007_Bistable 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 | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | Shared_Object_
Ajay_Bhalla_
2007_Bistable
Pathway No. : 363 | 9.9999
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.05(uM) | - | Substrate
GTP-Ras
craf-1*
Product
Raf*-GTP-Ras
| | Assume the binding is fast and limited only by the amount of Ras* available. 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 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 May 16, 2003 Changed Ras and Raf to synaptic levels, an increase of about 2x for each. To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold to 10. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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