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Molecule Parameter List for L.PDGFR | 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. |
L.PDGFR acting as a Molecule in mkp1_feedback_effects Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | L.PDGFR | mkp1_feedback_
effects
Accession No. : 4 | PDGFR
Pathway No. : 38 | 0 | 1000 | No | | This is terribly simplified: there are many interesting intermediate stages, including dimerization and assoc with adapter molecules like Shc, that contribute to the activation of the EGFR. |
L.PDGFR 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 | L.PDGFR /
phosph_Shc
| mkp1_feedback_
effects
Accession No. : 4 | PDGFR
Pathway No. : 38 | 0.833333 | 0.05 | 4 | explicit E-S complex | Substrate
SHC
Product
SHC*
| | Rates from Okada et al JBC 270:35 pp 20737 1995 Km = 0.70 to 0.85 uM, Vmax = 4.4 to 5.0 pmol/min. Unfortunately the amount of enzyme is not known, the prep is only partially purified. Tau phosph is max within 30 sec, falls back within 20 min. Ref: Sasaoka et al JBC 269:51 32621 1994. Use k3 = 0.1 based on this tau. 27 Apr 2001: Lowered k3 to 0.05 to fix conc-effect of SHC phosph by PDGF. This gives results for downstream effects in agreement with other papers, e.g., the Brondello papers. |
L.PDGFR 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 | | Internalize | mkp1_feedback_
effects
Accession No. : 4 | PDGFR
Pathway No. : 38 | 0.001
(s^-1) | 0.0007
(s^-1) | Keq = 0.66(uM) | 588.235sec | Substrate
L.PDGFR
Product
Internal_
L.PDGFR
| | Original model derived from EGFR model. See Helin and Beguinot JBC 266:13 1991 pg 8363-8368. In Fig 3 they have internalization tau about 10 min, equil at about 20% EGF available. So kf = 4x kb, and 1/(kf + kb) = 600 sec so kb = 1/3K = 3.3e-4, and kf = 1.33e-3. This doesn't take into account the unbound receptor, so we need to push the kf up a bit, to 0.002 26 apr 2001: Keq too low for the PDGF model. Now Kf=0.001,Kb=0.00066 The previously calculated internalization equilibrium led to very high internalization which shifted the effective dependence of the receptor on PDGF so it looked like the receptor binding was higher affinity than experimentally determined. Used two constraining factors: 1. Time course of SHC phosphorylation/dephosphorylation which is fast on, but 10-20 minutes off. 2. Conc dependence of MAPK on PDGF has a halfmax around 3ng/ml. See Brondello et al 1997 JBC 272(2):1368-1376 and Brondello et al 1999 Science 286:2514-1517. |
L.PDGFR 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 | | act_PDGFR | mkp1_feedback_
effects
Accession No. : 4 | PDGFR
Pathway No. : 38 | 199.998
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0005(uM) | - | Substrate
PDGF
PDGFR
Product
L.PDGFR
| | From Heidaran et al JBC268(13):9287 Fig 5. Kd is ~0.5 nM |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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