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Accession Type:
Network
Ajay_Bhalla_
2004_PKM_Tuning
PKC
Shared_Object_
Ajay_Bhalla_
2004_PKM_tuning
PLA2
PLCbeta
 Molecule
 Enzyme
 Reaction
Gq
MAPK
Ras
EGFR
Sos
PLC_g
CaMKII
CaM
PP1
PP2B
PKA
AC
PKM

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Reaction List for pathway PLCbeta (Pathway Number 315)

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-PLC-by-Gqkf
(uM^-1 s^-1)
1
(s^-1)
Kd(bf) = 0.0397(uM)-G*GTP
PLC-Ca
PLC-Ca-Gq
  Affinity for Gq is > 20 nM (Smrcka et al Science251 804-807 1991) so [Gq].kf = kb so 40nM * 6e5 = kb/kf = 24e3 so kf = 4.2e-5, kb =1
2 Act-PLC-Cakf
(uM^-1 s^-1)
1
(s^-1)
Kd(bf) = 0.3333(uM)-Ca
PLC
PLC-Ca
  Affinity for Ca = 1uM without AlF, 0.1 with: from Smrcka et al science 251 pp 804-807 1991 so [Ca].kf = kb so kb/kf = 1 * 6e5 = 1/1.66e-6 11 June 1996: Raised affinity to 5e-6 to maintain balance. See notes.
3 Degrade-DAGkf
(s^-1)
0
(s^-1)
Not applicable**-DAG
PC
  These rates are the same as for degrading IP3, but I am sure that they could be improved. Lets double kf to 0.2, since the amount of DAG in the cell should be <= 1uM. Need to double it again, for the same reason. kf now 0.5 27 June 1996 kf is now 0.02 to get 50 sec time course 30 Aug 1997: Raised kf to 0.11 to accomodate PLC_gamma 27 Mar 1998: kf now 0.15 for PLC_gamma
4 Degrade-IP3kf
(s^-1)
0
(s^-1)
--IP3
Inositol
  The enzyme is IP3 5-phosphomonesterase. about 45K. Actual products are Ins(1,4)P2, and cIns(1:2,4,5)P3. review in Majerus et al Science 234 1519-1526, 1986. Meyer and Stryer 1988 PNAS 85:5051-5055 est decay of IP3 at 1-3/sec
5 Inact-PLC-Gqkf
(s^-1)
0
(uM^-1 s^-1)
--PLC-Ca-Gq
G*GDP
PLC-Ca
  This process is assumed to be directly caused by the inactivation of the G*GTP to G*GDP. Hence, kf = .013 /sec = 0.8/min, same as the rate for Inact-G. kb = 0 since this is irreversible. We may be interested in studying the role of PLC as a GAP. If so, the kf would be faster here than in Inact-G
6 PLC-bind-Gqkf
(uM^-1 s^-1)
1
(s^-1)
Kd(bf) = 0.3968(uM)-PLC
G*GTP
PLC-Gq
  this binding does not produce active PLC. This step was needed to implement the described (Smrcka et al) increase in affinity for Ca by PLC once Gq was bound. The kinetics are the same as the binding step for Ca-PLC to Gq. June 1996: Changed the kf to 4.2e-5 to 4.2e-6 to preserve balance around the reactions.
7 PLC-Gq-bind-Cakf
(uM^-1 s^-1)
1
(s^-1)
Kd(bf) = 0.0333(uM)-Ca
PLC-Gq
PLC-Ca-Gq
  this step has a high affinity for Ca, from Smrcka et al. 0.1uM so kf /kb = 1/6e4 = 1.666e-5:1. See the Act-PLC-by-Gq reac. 11 Jun 1996: Raised kf to 5e-5 based on match to conc-eff curves from Smrcka et al.


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