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Ajay_Bhalla_
2004_PKM_MKP3_
Tuning
Shared_Object_
Ajay_Bhalla_
2004_PKM_MKP3_
Tuning
PKC
PLA2
PLCbeta
Ras
Gq
MAPK
EGFR
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 Enzyme
 Reaction
Sos
PLC_g
CaMKII
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Reaction List for pathway EGFR (Pathway Number 336)

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 act_EGFR4.2
(uM^-1 s^-1)
0.25
(s^-1)
Kd(bf) = 0.0595(uM)-EGFR
EGF
L.EGFR
  Affinity of EGFR for EGF is complex: depends on [EGFR]. We'll assume fixed [EGFR] and use exptal affinity ~20 nM (see Sherrill and Kyte Biochem 1996 35 5705-5718, Berkers et al JBC 266:2 922-927 1991, Sorokin et al JBC 269:13 9752-9759 1994). Tau =~2 min (Davis et al JBC 263:11 5373-5379 1988) or Berkers Kass = 6.2e5/M/sec, Kdiss=3.5e-4/sec. Sherrill and Kyte have Hill Coeff=1.7
2 dephosph_Shc0.0017
(s^-1)
0
(s^-1)
--SHC*
SHC
  Time course of decline of phosph is 20 min. Part of this is the turnoff time of the EGFR itself. Lets assume a tau of 10 min for this dephosph. It may be wildly off.
3 Internalize0.002
(s^-1)
0.0003
(s^-1)
Keq = 0.165(uM)434.783secL.EGFR
Internal_L.EGFR
  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


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