| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | Gs-bind-AC2* | AC
Pathway No. 85 | 833.28
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0012(uM) | - | Substrate:
Gs-alpha
AC2*
Products:
AC2*-Gs
|
| Various references: Jacobowitz et al JBC 268(6):3829-3892 show that AC2 has a 2x rise in basal activation on phosphorylation, and a 2x rise in forskolin stimulated activation. Yoshimura and Cooper JBC 1993 268(7):4604-4607 say that type II is stimulated 9x over basal. Lustig et al 1993 JBC 268(19):13900-13905 syow a 2x activation by PDBu, and the Gs stimulated response is increased 2x-4x by PDBu. To match all these results with the binding of the unphosphorylated form we use a Kd of 1.2 nM here as compared with the Kd of 2 nM for the unphosphorylated reaction. | | 2 | CaM_bind_PDE1 | AC
Pathway No. 85 | 720
(uM^-1 s^-1) | 5
(s^-1) | Kd(bf) = 0.0069(uM) | - | Substrate:
PDE1
CaM-Ca4
Products:
CaM.PDE1
|
| Borisy et al J Neurosci 12(3):915-923 For olf epithelium PDE1, affinity is 7 nM CaM and about 2 uM Ca which is consistent with it binding Ca4.CaM at 7 nM. Assume same for brain. Reaction should be pretty fast. Assume kb = 5/sec. | | 3 | Gs-bind-AC2 | AC
Pathway No. 85 | 499.998
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.002(uM) | - | Substrate:
AC2
Gs-alpha
Products:
AC2-Gs
|
| Half-max at around 3nM = kb/kf from fig 5 in Feinstein et al PNAS USA 88 10173-10177 1991 kf = kb/1800 = 5.56e-4 kb Ofer Jacobowitz's thesis data indicates it is more like 2 nM. Jacobowitz, PhD Thesis, Mount Sinai School of Medicine. | | 4 | Gs-bind-AC1 | AC
Pathway No. 85 | 126
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0079(uM) | - | Substrate:
Gs-alpha
AC1
Products:
AC1-Gs
|
| Half-max 8nM from Tang et al JBC266:13 8595-8603 kb/kf = 8 nM = 4800#/cell Also assume rapid binding of 1/sec. | | 5 | CaM-bind-AC1 | AC
Pathway No. 85 | 49.9998
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.02(uM) | - | Substrate:
CaM-Ca4
AC1
Products:
AC1-CaM
|
| Half-max at 20 nM CaM (Tang et al JBC 266:13 8595-8603 1991 Assume a rapid CaM binding of 1/sec. | | 6 | dephosph-AC2 | AC
Pathway No. 85 | 0.1
(s^-1) | 0
(s^-1) | - | - | Substrate:
AC2*
Products:
AC2
|
| Rate constrained by balancing levels of phosphorylated form, especially given resting PKC levels. | | 7 | dephosph-PDE | AC
Pathway No. 85 | 0.1
(s^-1) | 0
(s^-1) | - | - | Substrate:
cAMP-PDE*
Products:
cAMP-PDE
|
| The rates for this are poorly constrained. In adipocytes (probably a different PDE) the dephosphorylation is complete within 15 min, but there are no intermediate time points so it could be much faster. Identity of phosphatase is still unknown. |
and 
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