| |
Name | Pathway Name /
Pathway No. | Accession
Type | Initial
Conc.
(uM) | Volume
(fL) | Buffered | Sum Total Of |
| 1 | PKC-Ca | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | This intermediate is strongly indicated by the synergistic activation of PKC by combinations of DAG and Ca, as well as AA and Ca. PKC by definition also has a direct Ca-activation, to which this also contributes. |
| 2 | PKC-DAG-AA* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | Membrane translocated form of PKC-DAG-AA complex. |
| 3 | PKC-Ca-AA* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | Membrane bound and active complex of PKC, Ca and AA. |
| 4 | PKC-Ca-memb* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | This is the direct Ca-stimulated activity of PKC. |
| 5 | PKC-DAG-memb* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | Active, membrane attached form of Ca.DAG.PKC complex. |
| 6 | PKC-basal* | PKC
Pathway No. 71 | Network | 0.02 | 1000 | No | - |
| | This is the basal PKC activity which contributes about 2% to the maximum. |
| 7 | PKC-AA* | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | This is the membrane-bound and active form of the PKC-AA complex. |
| 8 | PKC-Ca-DAG | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | This is the active PKC form involving Ca and DAG. It has to translocate to the membrane. |
| 9 | PKC-DAG | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | This is a DAG-bound intermediate used in synergistic activation of PKC by DAG and AA. |
| 10 | PKC-DAG-AA | PKC
Pathway No. 71 | Network | 0 | 1000 | No | - |
| | Complex of PKC, DAG and AA giving rise to synergistic activation of PKC by DAG and AA at resting Ca. |
| 11 | PKC-cytosolic | PKC
Pathway No. 71 | Network | 1 | 1000 | No | - |
| | Marquez et al J. Immun 149,2560(92) est 1e6/cell for chromaffin cells Kikkawa et al 1982 JBC 257(22):13341 have PKC levels in brain at about 1 uM. The cytosolic form is the inactive PKC. This is really a composite of three isoforms: alpha, beta and gamma which have slightly different properties and respond to different combinations of Ca, AA and DAG. |
| 12 | DAG | Shared_Object_
Synaptic_
Network
Pathway No. 70Network | 0 | 1000 | No | - | |
| | Baseline in model is 11.661 uM. DAG is pretty nasty to estimate. In this model we just hold it fixed at this baseline level. Data sources are many and varied and sometimes difficult to reconcile. Welsh and Cabot 1987 JCB 35:231-245: DAG degradation Bocckino et al JBC 260(26):14201-14207: hepatocytes stim with vasopressin: 190 uM. Bocckino et al 1987 JBC 262(31):15309-15315: DAG rises from 70 to 200 ng/mg wet weight, approx 150 to 450 uM. Prescott and Majerus 1983 JBC 258:764-769: Platelets: 6 uM. Also see Rittenhouse-Simmons 1979 J Clin Invest 63. Sano et al JBC 258(3):2010-2013: Report a nearly 10 fold rise. Habenicht et al 1981 JBC 256(23)12329-12335: 3T3 cells with PDGF stim: 27 uM Cornell and Vance 1987 BBA 919:23-36: 10x rise from 10 to 100 uM. Summary: I see much lower rises in my PLC models, but the baseline could be anywhere from 5 to 100 uM. I have chosen about 11 uM based on the stimulus -response characteristics from the Schaechter and Benowitz paper and the Shinomura et al papers. |
| 13 | AA | Shared_Object_
Synaptic_
Network
Pathway No. 70Network | 0 | 1000 | No | - | |
| | Arachidonic Acid. This messenger diffuses through membranes as well as cytosolically, has been suggested as a possible retrograde messenger at synapses. |
| 14 | PLA2-cytosolic | PLA2
Pathway No. 72 | Network | 0.4 | 1000 | No | - |
| | cPLA2 IV form has mol wt of 85 Kd. Glaser et al 1993 TIPS 14:92-98. Calculated cytosolic concentration is ~300 nM from Wijkander and Sundler 1991 Eur J Biochem 202:873 Leslie and Channon 1990 BBA 1045:261 use about 400 nM. Decent match. Use 400 nM. |
| 15 | PLA2-Ca* | PLA2
Pathway No. 72 | Network | 0 | 1000 | No | - |
| | The generic Ca-activated form ofPLA2. Leslie and Channon 1990 BBA 1045:261. |
| 16 | PIP2-PLA2* | PLA2
Pathway No. 72 | Network | 0 | 1000 | No | - |
| | PLA2 activated by PIP2 alone. |
| 17 | PIP2-Ca-PLA2* | PLA2
Pathway No. 72 | Network | 0 | 1000 | No | - |
| | Activated form of PLA2 with PIP2 and Ca bound. |
| 18 | DAG-Ca-PLA2* | PLA2
Pathway No. 72 | Network | 0 | 1000 | No | - |
| | Active form of PLA2 with DAG and Ca bound. DAG and Ca act in combination hence the need for this form in the model. Leslie and Channon (199) BBA 1045:261-270 |
| 19 | PLA2*-Ca | PLA2
Pathway No. 72 | Network | 0 | 1000 | No | - |
| | Phosphorylated and active form of PLA2. Several kinases act on it: PKA: Wightman et al JBC 257 pp6650 1982 PKC: Many refs, eg Gronich et al JBC 263 pp 16645, 1988 but see Lin etal MAPK: Lin et al, Cell 72 pp 269, 1993. Show 3x with MAPK but not PKC alone The Nemenoff assays are conducted in rather high Ca so I have assumed a Ca binding step. |
| 20 | PLA2* | PLA2
Pathway No. 72 | Network | 0 | 1000 | No | - |
| | Phosphorylated PLA2. The site differs from the site phosphorylated by PKC. See Nemenoff et al 1993 JBC 268(3):1960-1964 |
and 
color.