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Molecule Parameter List for PKC-active

The statistics table lists the distribution of a molecule acting either as a substrate, product, enzyme or as a molecule within the network.
The text color of a molecule is highlighted by

color.

Statistics

*PKC-active* participated as	Molecule	Sum total of	Enzyme	Substrate of an enzyme	Product of an enzyme	Substrate in Reaction	Product in Reaction
No. of occurrences	1	1	6	0	0	0	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
Ajay_Bhalla_ 2004_Feedback_ Tuning	78	Network	Shared_Object_Ajay_Bhalla_2004_Feedback_Tuning, PKC, PLA2, PLCbeta, Gq, MAPK, Ras, EGFR, Sos, PLC_g, CaMKII, CaM, PP1, PP2B, PKA, AC
This model is taken from Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80. This is the feedback model from Figure 8a.

PKC-active acting as a Molecule in Ajay_Bhalla_2004_Feedback_Tuning Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
PKC-active	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	Shared_Object_ Ajay_Bhalla_ 2004_Feedback_ Tuning Pathway No. : 347	0	1.5	No

PKC-active acting as a Summed Molecule in Ajay_Bhalla_2004_Feedback_Tuning Network

Accession Name	Pathway Name	Target	Input
Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	Shared_Object_ Ajay_Bhalla_ 2004_Feedback_ Tuning Pathway No. : 347	PKC-active	PKC-DAG-AA* PKC-Ca-memb* PKC-Ca-AA* PKC-DAG-memb* PKC-basal* PKC-AA*

PKC-active acting as an Enzyme in Ajay_Bhalla_2004_Feedback_Tuning Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	PKC-active / PKC-act-raf	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	Shared_Object_ Ajay_Bhalla_ 2004_Feedback_ Tuning Pathway No. : 347	66.6673	4	4	explicit E-S complex	Substrate craf-1 Product craf-1*
	Rate consts from Chen et al Biochem 32, 1032 (1993) k3 = k2 = 4 k1 = 9e-5 recalculated gives 1.666e-5, which is not very different. Looks like k3 is rate-limiting in this case: there is a huge amount of craf locked up in the enz complex. Let us assume a 10x higher Km, ie, lower affinity. k1 drops by 10x. Also changed k2 to 4x k3. Lowerd k1 to 1e-6 to balance 10X DAG sensitivity of PKC
2	PKC-active / PKC-inact-GAP	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	Shared_Object_ Ajay_Bhalla_ 2004_Feedback_ Tuning Pathway No. : 347	3.33332	4	4	explicit E-S complex	Substrate GAP Product GAP*
	Rate consts copied from PCK-act-raf This reaction inactivates GAP. The idea is from the Boguski and McCormick review.
3	PKC-active / PKC-act-GEF	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	Shared_Object_ Ajay_Bhalla_ 2004_Feedback_ Tuning Pathway No. : 347	3.33332	4	4	explicit E-S complex	Substrate inact-GEF Product GEF*
	Rate consts from PKC-act-raf. This reaction activates GEF. It can lead to at least 2X stim of ras, and a 2X stim of MAPK over and above that obtained via direct phosph of c-raf. Note that it is a push-pull reaction, and there is also a contribution through the phosphorylation and inactivation of GAPs. The original PKC-act-raf rate consts are too fast. We lower K1 by 10 X
4	PKC-active / PKC-phosph-neuro granin	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	Shared_Object_ Ajay_Bhalla_ 2004_Feedback_ Tuning Pathway No. : 347	28.6283	0.58	4.03448	explicit E-S complex	Substrate neurogranin Product neurogranin*
	Rates from Huang et al ABB 305:2 570-580 1993
5	PKC-active / PKC-phosph-ng-Ca M	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	Shared_Object_ Ajay_Bhalla_ 2004_Feedback_ Tuning Pathway No. : 347	28.5948	0.35	4	explicit E-S complex	Substrate neurogranin-CaM Product CaM neurogranin*
	Rates are 60% those of PKC-phosph-neurogranin. See Huang et al ABB 305:2 570-580 1993
6	PKC-active / phosph-AC2	Ajay_Bhalla_ 2004_Feedback_ Tuning Accession No. : 78	Shared_Object_ Ajay_Bhalla_ 2004_Feedback_ Tuning Pathway No. : 347	33.3332	4	4	explicit E-S complex	Substrate AC2 Product AC2*
	Phorbol esters have little effect on AC1 or on the Gs-stimulation of AC2. So in this model we are only dealing with the increase in basal activation of AC2 induced by PKC k1 = 1.66e-6 k2 = 16 k3 =4

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