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Reaction List for pathway PDGFR (Pathway Number 38) in Accession mkp1_feedback_effects (Accession Number 4)

Entries are grouped according to Pathway Number and they are alternately color coded using  and  color.
Further ordering can be done to the table header.  indicates that ordering is done according to ascending or descending order.
Keq is calculated only for first order reactions.
Kd is calculated only for second order reactions. [nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules]
  Reaction
Name
Pathway Name / 
Pathway No.
KfKbKdtauReagents
1 act_PDGFRPDGFR

Pathway No. 38
199.998
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 0.0005(uM)-  Substrate:
 PDGFR
 PDGF

 Products:
 L.PDGFR
  From Heidaran et al JBC268(13):9287 Fig 5. Kd is ~0.5 nM
2 dephosph_ShcPDGFR

Pathway No. 38
0.01
(s^-1)
0
(s^-1)
--  Substrate:
 SHC*

 Products:
 SHC
  Time course of decline of phosph is 20 min from Sasaoka et al 1994 JBC 269(51):32621. Part of this is the turnoff time of the EGFR itself. Lets assume a tau of 10 min for this dephosphorylation as a first pass. 27 Apr 2001: Dephosph too slow, shifts SHC balance over to phosphorylated form. Increase Kf to 0.01. This gives a reasonable overall time-course.
3 InternalizePDGFR

Pathway No. 38
0.001
(s^-1)
0.0007
(s^-1)
Keq = 0.66(uM)588.235sec  Substrate:
 L.PDGFR

 Products:
  •  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.

     
    Result: 1 - 3 of 3 rows are displayed



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