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Accession Type:
Network
Ajay_Bhalla_
2007_ReacDiff3
Shared_Object_
Ajay_Bhalla_
2007_ReacDiff3
PKC
PLA2
MAPK
PLA2
Ras
CaM
chain
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3
PKC
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[1]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[2]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[3]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[4]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[5]
PKC
PLA2
MAPK
Ras
MAPK
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[6]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[7]
PKC
PLA2
MAPK
Ras
CaM
PKC
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[8]
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[9]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[10]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[11]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[12]
PKC
PLA2
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[13]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[14]
 Molecule
 Enzyme
 Reaction
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[15]
PKC
PLA2
MAPK
Ras
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[16]
CaM
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[17]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[18]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[19]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[20]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[21]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[22]
PKC
PLA2
MAPK
Ras
CaM
Shared Object_
Ajay_Bhalla_
2007_ReacDiff3_
[23]
PKC
PLA2
MAPK
Ras
CaM

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Enzyme List for pathway Shared Object_Ajay_Bhalla_2007_ReacDiff3[14] (Pathway Number 1009)

 Molecule Name/
Site Name
Km (uM) kcat (1/s)Ratio
(k2/k3)
Enzyme TypeSubstrate Product
1 Enzyme Activity:
craf**-deph

Enzyme Molecule:
PPhosphatase2A
15.656764explicit E-S complexcraf-1**
craf-1*
  Ueki et al JBC 269(22) pp 15756-15761 1994 show hyperphosphorylation of craf, so this is there to dephosphorylate it. Identity of phosphatase is not known to me, but it may be PP2A like the rest, so I have made it so.
2 Enzyme Activity:
craf-deph

Enzyme Molecule:
PPhosphatase2A
15.656764explicit E-S complexcraf-1*
craf-1
  See parent PPhosphatase2A for parms
3 Enzyme Activity:
MAPK*

Enzyme Molecule:
MAPK*
25.6405104explicit E-S complexPLA2-cytosolic
PLA2*
  Km = 25uM @ 50 uM ATP and 1mg/ml MBP (huge XS of substrate) Vmax = 4124 pmol/min/ml at a conc of 125 pmol/ml of enz, so: k3 = .5/sec (rate limiting) k1 = (k2 + k3)/Km = (.5 + 0)/(25*6e5) = 2e-8 (#/cell)^-1 #s from Sanghera et al JBC 265 pp 52 , 1990. From Nemenoff et al JBC 268(3):1960-1964 - using Sanghera's 1e-4 ratio of MAPK to protein, we get k3 = 7/sec from 1000 pmol/min/mg fig 5
4 Enzyme Activity:
MAPK*-feedback

Enzyme Molecule:
MAPK*
25.6405104explicit E-S complexcraf-1*
craf-1**
  Ueki et al JBC 269(22):15756-15761 show the presence of this step, but not the rate consts, which are derived from Sanghera et al JBC 265(1):52-57, 1990, see the deriv in the MAPK* notes.
5 Enzyme Activity:
MAPKK-deph

Enzyme Molecule:
PPhosphatase2A
15.656764explicit E-S complexMAPKK*
MAPKK-ser
  See: Kyriakis et al Nature 358 pp 417-421 1992 Ahn et al Curr Op Cell Biol 4:992-999 1992 for this pathway. See parent PPhosphatase2A for parms.
6 Enzyme Activity:
MAPKK-deph-ser

Enzyme Molecule:
PPhosphatase2A
15.656764explicit E-S complexMAPKK-ser
MAPKK
 
7 Enzyme Activity:
MKP1-thr-deph

Enzyme Molecule:
MKP-1
0.13333344explicit E-S complexMAPK*
MAPK-tyr
  See MKP1-tyr-deph
8 Enzyme Activity:
MKP1-tyr-deph

Enzyme Molecule:
MKP-1
0.13333344explicit E-S complexMAPK-tyr
MAPK
  The original kinetics have been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. As noted in the NOTES, the only constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. It would be nice to have more accurate estimates of rate consts and MKP-1 levels from the literature. Effective Km : 67 nM kcat = 1.43 umol/min/mg
9 Enzyme Activity:
PKC-act-GEF

Enzyme Molecule:
PKC-active
3.3333344explicit E-S complexinact-GEF
GEF*
  Rate consts from PKC-act-raf. This reaction activates GEF. It can lead to at least 2X stim of ras, and a 2X stim of MAPK over and above that obtained via direct phosph of c-raf. Note that it is a push-pull reaction, and there is also a contribution through the phosphorylation and inactivation of GAPs. The original PKC-act-raf rate consts are too fast. We lower K1 by 10 X
10 Enzyme Activity:
PKC-act-raf

Enzyme Molecule:
PKC-active
66.666544explicit E-S complexcraf-1
craf-1*
  Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = k2 = 4 k1 = 9e-5 recalculated gives 1.666e-5, which is not very different. Looks like k3 is rate-limiting in this case: there is a huge amount of craf locked up in the enz complex. Let us assume a 10x higher Km, ie, lower affinity. k1 drops by 10x. Also changed k2 to 4x k3. Lowerd k1 to 1e-6 to balance 10X DAG sensitivity of PKC
11 Enzyme Activity:
PKC-inact-GAP

Enzyme Molecule:
PKC-active
3.3333344explicit E-S complexGAP
GAP*
  Rate consts copied from PCK-act-raf This reaction inactivates GAP. The idea is from the Boguski and McCormick review.


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Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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