| |
Name | Pathway Name /
Pathway No. | Accession
Type | Initial
Conc.
(uM) | Volume
(fL) | Buffered | Sum Total Of |
| 1 | tot_CaM_CaMKII | CaMKII
Pathway No. 80 | Network | 0 | 1000 | No | CaMKII-CaM
CaMKII-thr286*-C
aM
|
| | This pool sums the levels of the CaM-bound forms of CaMKII: CaMKII-CaM + CaMKII-thr286*-CaM. Although their phosphorylation states are different, the level of activity is about the same so it makes sense to sum the levels. Hanson et al 1994 Neuron 12:943-956 |
| 2 | tot_autonomous_
CaMKII | CaMKII
Pathway No. 80 | Network | 0 | 1000 | No | CaMKII-thr286
CaMKII***
|
| | This is the sum total of the various CaM-independent forms of the kinase. There are actually several possible states here, but I only consider the forms thr-286 phosphorylated form and the doubly/triply phosphorylated form including the thr305/306, represented here as CaMKII*** |
| 3 | total-CaMKII | CaMKII
Pathway No. 80 | Network | 70 | 1000 | Yes | - |
| | This pool is purely here to provide a single, fixed number, which is the total amount of CaMKII. This is used by the autophosphorylation steps to scale down the rates so that the autophosphorylation reactions are independent of CaMKII levels. |
| 4 | temp-PIP2 | Shared_Object_
Synaptic_
Network
Pathway No. 70Network | 2.5 | 1000 | Yes | - | |
| | This is a steady PIP2 input to PLA2. The sensitivity of PLA2 to PIP2 discussed below does not match with the reported free levels which are used by the phosphlipase Cs. My understanding is that there may be different pools of PIP2 available for stimulating PLA2 as opposed to being substrates for PLCs. For that reason I have given this PIP2 pool a separate identity. As it is a steady input this is not a problem in this model. Majerus et al Cell 37:701-703 report a brain concentration of 0.1 - 0.2 mole % Majerus et al Science 234:1519-1526 report a huge range of concentrations: from 1 to 10% of PI content, which is in turn 2-8% of cell lipid. This gives 2e-4 to 8e-3 of cell lipid. In concentrations in total volume of cell (a somewhat strange number given the compartmental considerations) this comes to anywhere from 4 uM to 200 uM. PLA2 is stim 7x by PIP2 (Leslie and Channon BBA 1045:261(1990) Leslie and Channon say PIP2 is present at 0.1 - 0.2mol% range in membs, so I'll use a value at the lower end of the scale for basal PIP2. |
| 5 | synapse | Shared_Object_
Synaptic_
Network
Pathway No. 70Network | 0 | 1000 | No | - | |
| | A pool representing the presynaptic terminal and release of glutamate. It is controlled by the temporal pattern of the synaptic input. |
| 6 | Sos.Grb2 | Sos
Pathway No. 78 | Network | 0 | 1000 | No | - |
| | For simplicity I treat the activation of Sos as involving a single complex comprising Sos, Grb2 and Shc*. This is reasonably documented: Sasaoka et al 1994 JBC 269(51):32621-5 Chook et al JBC 1996 271(48):30472 |
| 7 | Sos*.Grb2 | Sos
Pathway No. 78 | Network | 0 | 1000 | No | - |
| | Inactive complex of Sos* with Grb2 due to phosphorylation of the Sos. See Porfiri and McCormick 1996 JBC 271(10):5871. |
| 8 | Sos* | Sos
Pathway No. 78 | Network | 0 | 1000 | No | - |
| | Phosphorylated form of SoS. Nominally this is an inactivation step mediated by MAPK, see Profiri and McCormick 1996 JBC 271(10):5871. I have not put this inactivation in this pathway so this molecule currently only represents a potential interaction point. |
| 9 | Sos | Sos
Pathway No. 78 | Network | 0.1 | 1000 | No | - |
| | I have tried using low (0.02 uM) initial concs, but these give a very flat response to EGF stim although the overall activation of Ras is not too bad. I am reverting to 0.1 because we expect a sharp initial response, followed by a decline. |
| 10 | Shc*.Sos.Grb2 | Shared_Object_
Synaptic_
Network
Pathway No. 70Network | 0 | 1000 | No | - | |
| | This three-way complex is one of the main GEFs for activating Ras. |
| 11 | SHC* | EGFR
Pathway No. 77 | Network | 0 | 1000 | No | - |
| | Phosphorylated form of SHC. Binds to the Sos.Grb2 complex to give the activated GEF form upstream of Ras. |
| 12 | SHC | EGFR
Pathway No. 77 | Network | 0.5 | 1000 | No | - |
| | There are 2 isoforms: 52 KDa and 46 KDa (See Okada et al JBC 270:35 pp 20737 1995). They are acted up on by the EGFR in very similar ways, and apparently both bind Grb2 similarly, so we'll bundle them together here. Sasaoka et al JBC 269:51 pp 32621 1994 show immunoprecs where it looks like there is at least as much Shc as Grb2. So we'll tentatively say there is 0.5 uM of Shc. |
| 13 | Rec-Gq | Gq
Pathway No. 74 | Network | 0 | 1000 | No | - |
| | Turns out that a large fraction of the the receptor binds to the G-protein even in the absence of ligand. This pool represents this step. Fraction of Rec-Gq is 44% of receptor, from Fay et al 1991 Biochem 30:5066-5075 Since this is not the same receptor, this value is a bit doubtful. Still, we adjust the rate consts in Rec-bind-Gq to match. |
| 14 | Rec-Glu-Gq | Gq
Pathway No. 74 | Network | 0 | 1000 | No | - |
| | This is the ternary complex of receptor, ligand and G protein. |
| 15 | Rec-Glu | Gq
Pathway No. 74 | Network | 0 | 1000 | No | - |
| | Glu-Receptor complex. |
| 16 | Raf-GTP-Ras* | MAPK
Pathway No. 75 | Network | 0 | 1000 | No | - |
| | This is the main activated form of craf. It really refers to the complex of GTP-Ras with phosphorylated Raf. See Leevers 1994 Nature 369:411-414 and Hallberg et al 1994 JBC 269(6):3913-3916. The naming is a bit awkward but kept in this model for consistency with previous models (Bhalla and Iyengar 1999 Science 283:381-387) |
| 17 | R2C2-cAMP4 | PKA
Pathway No. 84 | Network | 0 | 1000 | No | - |
| | All the regulatory subunits now have cAMP bound. This state is ready to dissociate and to release the catalytic subunit. |
| 18 | R2C2-cAMP3 | PKA
Pathway No. 84 | Network | 0 | 1000 | No | - |
| | 3 cAMPs now bound. |
| 19 | R2C2-cAMP2 | PKA
Pathway No. 84 | Network | 0 | 1000 | No | - |
| | One cAMP bound to each of the B sites on the regulatory subunits. |
| 20 | R2C2-cAMP | PKA
Pathway No. 84 | Network | 0 | 1000 | No | - |
| | One cAMP bound to site B1 on the regulatory subunits. |
and 
color.