| |
Name | Accession
Type | Initial
Conc.
(uM) | Volume
(fL) | Buffered | Sum Total Of |
| 1 | Ubiquitination | Network | 0 | 0 | Yes | - |
| | This is a representation of generic ubiquitination followed by degradation. Since this pool is buffered to zero, anything that ends up here is removed from the model. |
| 2 | RGR | Network | 0 | 0 | No | - |
| | Shorthand name for Raf.GTP.Ras. This refers to the complex between GTP.Ras and the unphosphorylated Raf. I treat this as having the same enzyme activity as the Raf*.GTP.Ras form. |
| 3 | Raf*-GTP-Ras | Network | 0 | 0 | No | - |
| | This is the main activated form of craf. It requires binding to ras for activation, but the presence of the phosphorylation increases this binding. See Leevers 1994 Nature 369:411-414 and Hallberg et al 1994 JBC 269(6):3913-3916 |
| 4 | nuc_MAPK* | Network | 0 | 0 | No | - |
| | Cytoplasmic MAPK declines 20%, nuclear MAPK rises 100%. Furuno et al J Immunol 166:4416 (2001) Assume nuc vol 1/5 that of cytoplasm so nuc vol = 2e-16 Note therefore that the concentrations here will be higher for the same number of molecules. |
| 5 | Nucleotides | Network | 0.1 | 0 | Yes | - |
| | Infinite supply assumed for formation of mRNA. |
| 6 | MKP1-RNA | Network | 0.0001 | 0 | No | - |
| | The MKP-1 RNA is treated as the rate-limiting quantity for synthesis of MKP-1. |
| 7 | MKP-1-ser359* | Network | 0 | 0 | No | - |
| | Singly phosphorylated form of MKP-1. Slower ubiquitination. See Brondello et al 1999 Science 286:2514 From the simulations, this form has a rather low and transient level. So I do not include it in the dephosphorylation of MAPK. |
| 8 | MKP-1** | Network | 0 | 0 | No | - |
| | Same enzyme activity as MKP-1, but different degradation rates. Brondello et al Science 286:2514 1999 This form is doubly phosphorylated. |
| 9 | MAPKK-ser | Network | 0 | 0 | No | - |
| | Intermediately phophorylated, assumed inactive, form of MAPKK |
| 10 | MAPKK* | Network | 0 | 0 | No | - |
| | MAPKK phosphorylates MAPK on both the tyr and thr residues, first tyr then thr. Refs: Seger et al JBC267:20 pp 14373 1992 The MAPKK itself is phosphorylated on ser as well as thr residues. Let us assume that the ser goes first, and that the sequential phosphorylation is needed. See Kyriakis et al Nature 358 417-421 1992 |
| 11 | MAPKK | Network | 0.18 | 0 | No | - |
| | Conc is from Seger et al JBC 267:20 pp14373 (1992) mwt is 45/46 Kd We assume that phosphorylation on both ser and thr is needed for activiation. See Kyriakis et al Nature 358 417 1992 Init conc of total is 0.18 |
| 12 | MAPK-tyr | Network | 0 | 0 | No | - |
| | Haystead et al FEBS Lett. 306(1) pp 17-22 show that phosphorylation is strictly sequential, first tyr185 then thr183. |
| 13 | MAPK | Network | 0.36 | 0 | No | - |
| | Mol wt is 42 KDa. conc is from Sanghera et al JBC 265 pp 52 (1990) They estimate MAPK is 1e-4x total protein, and protein is 15% of cell wt, so MAPK is 1.5e-5g/ml = 0.36uM. Lets use this. Note though that Huang and Ferrell 1996 PNAS 93(19):10078 report 1.2 uM in oocytes. Also note that brain concs may be high. Ortiz et al 1995 J. Neurosci 15(2):1285-1297 report 0.3 ng/ug protein in Cingulate Gyrus and 1.2 ng/ug protein in nucleus accumbens. In hippocampus 270 ng/mg protein for ERK1 and 820 ng/mg protein for ERK 2. If 15% of cell weight is protein, that means that about 300 * 0.15 ng/ul is ERK 1. ie, 45e-9g/1e-6 litre = 45 mg/litre or about 1 uM. For non-neuronal tissues a lower value may be better. |
| 14 | craf-1** | Network | 0 | 0 | No | - |
| | Negative feedback by MAPK* by hyperphosphorylating craf-1* gives rise to this pool. Ueki et al JBC 269(22):15756-15761, 1994 |
| 15 | craf-1* | Network | 0 | 0 | No | - |
| | Singly phosphorylated form of c-raf-1. This is the form that gets best activated by GTP.Ras. |
| 16 | craf-1 | Network | 0.2 | 0 | No | - |
| | Strom et al 1990 Oncogene 5 pp 345-51 report high general expression in all tissues. Huang and Ferrell 1996 PNAS 93(19):10078 use a value of 3 nM for oocytes. Here we stick with a much higher expression based on the Strom report. |
and 
color.