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Molecule Parameter List for craf-1* | 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. |
craf-1* acting as a Molecule in mkp1_feedback_effects Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | craf-1* | mkp1_feedback_
effects
Accession No. : 4 | MAPK
Pathway No. : 35 | 0 | 1000 | No | | Singly phosphorylated form of c-raf-1. This is the form that gets best activated by GTP.Ras. |
craf-1* 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 | | 1 | MAPK* /
MAPK*-feedback | mkp1_feedback_
effects
Accession No. : 4 | Shared_Object_
mkp1_feedback_
effects
Pathway No. : 32 | 25.641 | 10 | 4 | explicit E-S complex | Substrate
craf-1*
Product
craf-1**
| | | Ueki K, Matsuda S, Tobe K, Gotoh Y, Tamemoto H, Yachi M, Akanuma Y, Yazaki Y, Nishida E, Kadowaki T. (1994) J Biol Chem. 269(22):15756-15761 show the presence of this step, but not the rate constants, which are derived from Sanghera JS, Paddon HB, Bader SA, Pelech SL. (1990) J Biol Chem. 265(1):52-57; follow the derivation in the MAPK* notes. | | 2 | PPhosphatase2A /
craf-deph | mkp1_feedback_
effects
Accession No. : 4 | Shared_Object_
mkp1_feedback_
effects
Pathway No. : 32 | 15.6566 | 6 | 4.16667 | explicit E-S complex | Substrate
craf-1*
Product
craf-1
| | | See parent PPhosphatase2A for parms |
craf-1* acting as a Product of an Enzyme in mkp1_feedback_effects Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | PKC-active /
PKC-act-raf | mkp1_feedback_
effects
Accession No. : 4 | Shared_Object_
mkp1_feedback_
effects
Pathway No. : 32 | 66.6667 | 4 | 4 | explicit E-S complex | Substrate
craf-1
Product
craf-1*
| | | Rate constants are from Chen SJ, Klann E, Gower MC, Powell CM, Sessoms JS, Sweatt JD. (1993) Biochemistry 32(4):1032-1039. k3 = 4 Km for this substrate is trickier. Specific substrates are in the uM range, so we use a higher Km here. This may be too conservative in which case PKC would have a still higher effect on raf. The presence of this phosphorylation and activation step is from Kolch W, Heidecker G, Kochs G, Hummel R, Vahidi H, Mischak H, Finkenzeller G, Marme D, Rapp UR. (1993) Nature 364(6434):249-52. | | 2 | PPhosphatase2A /
craf**-deph | mkp1_feedback_
effects
Accession No. : 4 | Shared_Object_
mkp1_feedback_
effects
Pathway No. : 32 | 15.6566 | 6 | 4.16667 | explicit E-S complex | Substrate
craf-1**
Product
craf-1*
| | | Ueki K, Matsuda S, Tobe K, Gotoh Y, Tamemoto H, Yachi M, Akanuma Y, Yazaki Y, Nishida E, Kadowaki T. (1994) J Biol Chem. 269(22):15756-61show hyperphosphorylation of craf, so this is there to dephosphorylate it. Identity of phosphatase is assumed to be PP2A. |
craf-1* 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 | | 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 |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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