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Molecule Parameter List for 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) |
GTP-Ras acting as a Molecule in Ajay_Bhalla_2007_Bistable Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | GTP-Ras | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | Ras
Pathway No. : 367 | 0 | 125.7 | No | | Only a very small fraction (7% unstim, 15% stim) of ras is GTP-bound. Gibbs et al JBC 265(33) 20437 |
GTP-Ras acting as a Substrate for 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 | GAP /
GAP-inact-ras | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | Ras
Pathway No. : 367 | 1.0104 | 10 | 4 | 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%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) 5 Nov 2002: Changed ratio term to 4 from 100. Now we have k1=8.25e-5; k2=40, k3=10. k3 is still rate-limiting. |
GTP-Ras acting as a Product of an Enzyme in Ajay_Bhalla_2007_Bistable Network
GTP-Ras acting as a Substrate 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 | | 1 | 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. | | 2 | Ras-intrinsic-GT
Pase | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | Ras
Pathway No. : 367 | 0.0001
(s^-1) | 0
(s^-1) | - | - | Substrate
GTP-Ras
Product
GDP-Ras
| | | This is extremely slow (1e-4), but it is significant as so little GAP actually gets complexed with it that the total GTP turnover rises only by 2-3 X (see Gibbs et al, JBC 265(33) 20437-20422) and Eccleston et al JBC 268(36) 27012-27019 kf = 1e-4 | | 3 | Ras-act-unphosph
-raf | Ajay_Bhalla_
2007_Bistable
Accession No. : 79 | Shared_Object_
Ajay_Bhalla_
2007_Bistable
Pathway No. : 363 | 6
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.1667(uM) | - | Substrate
GTP-Ras
craf-1
Product
Raf-GTP-Ras
| | | 18 May 2003. This reaction is here to provide basal activity for MAPK as well as the potential for direct EGF stimulus without PKC activation. Based on model from FB/fb28c.g: the model used for MKP-1 turnover. The rates there were constrained by basal activity values. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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