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Accession Type:
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mkp1_feedback_
effects
Shared_Object_
mkp1_feedback_
effects
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PKC
MAPK
PLA2
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Ras
PDGFR

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Reaction List for pathway PLA2 (Pathway Number 36)

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 reactions is not considered.
  Name KfKbKdtauSubstrateProduct
1 DAG-Ca-PLA2-act0.003
(uM^-1 s^-1)
4
(s^-1)
Kd(bf) = 1333.3333(uM)-DAG
PLA2-Ca*
DAG-Ca-PLA2*
  Synergistic activation of PLA2 by Ca and DAG. Based on Leslie and Channon 1990 BBA 1045:261 The Kd is rather large and may reflect the complications in measuring DAG. For this model it is not critical since DAG is held fixed.
2 Degrade-AA0.4
(s^-1)
0
(s^-1)
--AA
APC
  Degradation pathway for AA. APC is a convenient buffered pool to dump it back into, though the actual metabolism is probably far more complex. For the purposes of the full model we use a rate of degradation of 0.4/sec to give a dynamic range of AA comparable to what is seen experimentally. Wijkander and Sundler 1991 Eur J Biochem 202:873 Leslie and Channon 1990 BBA 1045:261
3 dephosphorylate-
PLA2*
0.17
(s^-1)
0
(s^-1)
--PLA2*
PLA2-cytosolic
  Dephosphorylation reaction to balance MAPK phosphorylation of PLA2. This is probably mediated by PP2A. Rates determined to keep the balance of phosphorylated and non-phosphorylated PLA2 reasonable. The constraining factor is the fold activation of PLA2 by MAPK.
4 PIP2-Ca-PLA2-act0.012
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 8.3333(uM)-temp-PIP2
PLA2-Ca*
PIP2-Ca-PLA2*
  Synergistic activation of PLA2 by Ca and PIP2. Again from Leslie and Channon 1990 BBA 1045:261
5 PIP2-PLA2-act0.0012
(uM^-1 s^-1)
0.5
(s^-1)
Kd(bf) = 416.6667(uM)-temp-PIP2
PLA2-cytosolic
PIP2-PLA2*
  Activation of PLA2 by PIP2. From Leslie and Channon 1990 BBA 1045:261 the stimulation of PLA2 activity by high PIP2 is 7x. In this model we don't really expect any PIP2 stimulus.
6 PLA2*-Ca-act6
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 0.0167(uM)-PLA2*
Ca
PLA2*-Ca
  Nemenoff et al 1993 JBC 268:1960 report a 2X to 4x activation of PLA2 by MAPK, which seems dependent on Ca as well. This reaction represents this activation. Rates are scaled to give appropriate fold activation.
7 PLA2-Ca-act1
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 0.1(uM)-PLA2-cytosolic
Ca
PLA2-Ca*
  Direct activation of PLA2 by Ca. From Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.


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