|
Enter a Search String | | Special character and space not allowed in the query term.
Search string should be at least 2 characters long. |
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 | 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. |
GTP-Ras acting as a Molecule in mkp1_feedback_effects Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | GTP-Ras | mkp1_feedback_
effects
Accession No. : 4 | Ras
Pathway No. : 37 | 0 | 1000 | 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 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. |
GTP-Ras acting as a Product of an Enzyme in mkp1_feedback_effects Network
GTP-Ras acting as a Substrate 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 | | 1 | 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 | | 2 | Ras-intrinsic-GT
Pase | mkp1_feedback_
effects
Accession No. : 4 | Ras
Pathway No. : 37 | 0.0001
(s^-1) | 0
(s^-1) | - | - | Substrate
GTP-Ras
Product
GDP-Ras
| | | This is extremely slow (kf = 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 There is no back reaction as we assume this to be a regular irreversible Michaelis-Menten zeroth order hydrolysis. | | 3 | Ras-act-unphosph
-raf | mkp1_feedback_
effects
Accession No. : 4 | Shared_Object_
mkp1_feedback_
effects
Pathway No. : 32 | 6
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.1667(uM) | - | Substrate
GTP-Ras
craf-1
Product
RGR
| | | Based on rates of Ras-act-craf which has Kf=60, Kb= 0.5. This reaction was introduced to account for the PKC-independent activation of MAPK. This reac should have less affinity but similar tau as compared to the Ras-cat-craf, since the phosphorylated Raf form has a greater effect on MAPK. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
This Copyright is applied to ensure that the contents of this database remain freely available. Please see FAQ for details. |
|
