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Molecule Parameter List for DAG | 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 |
| DAG 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 | 0 | 0 | 0 | 0 | 3 | 0 |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | mkp1_feedback_
effects | 4 | Network |
Shared_Object_mkp1_feedback_effects, Sos, PKC,
MAPK, PLA2, Ras,
PDGFR | | This is a network involving the MAPK-PKC feedback loop with input from the PDGFR in the synapse. The distinctive feature of this model is that it includes MKP-1 induction by MAPK, and the consequent inhibitory regulation of MAPK and the feedback loop. Lots of interesting dynamics arise from this. This link provides supplementary material for the paper Bhalla US et al. Science (2002) 297(5583):1018-23. In the form of several example simulations and demos for the figures in the paper. |
DAG acting as a Molecule in mkp1_feedback_effects Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | DAG | mkp1_feedback_
effects
Accession No. : 4 | Shared_Object_
mkp1_feedback_
effects
Pathway No. : 32 | 11.661 | 1000 | Yes | 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 CJ and Cabot MC (1987) J Cell Biochem. 35(3):231-245. DAG degradation Bocckino SB, Blackmore PF, Exton JH. (1985) J Biol Chem. 260(26):14201-14207. Hepatocytes stimulated with vasopressin: 190 uM. Bocckino SB, Blackmore PF, Wilson PB, Exton JH. (1987) J Biol Chem. 262(31):15309-15. DAG rises from 70 to 200 ng/mg wet weight, approx 150 to 450 uM. Prescott SM and Majerus PW. (1983) J Biol Chem. 258(2):764-769. Platelets: 6 uM. Also see Rittenhouse-Simmons S. (1979) J Clin Invest. 63(4):580-587. Sano K, Takai Y, Yamanishi J, Nishizuka Y. (1983) J Biol Chem. 258(3):2010-2013. report a nearly 10 fold rise. Habenicht AJ, Glomset JA, King WC, Nist C, Mitchell CD, Ross R. (1981) J Biol Chem. 256(23):12329-35. 3T3 cells with PDGF stim: 27 uM. Cornell R and Vance DE. (1987) Biochim Biophys Acta. 1987 May 13;919(1):26-36. 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 Schaechter JD and Benowitz LI. (1993) J Neurosci. 13(10):4361-4371 and Shinomura T, Asaoka Y, Oka M, Yoshida K, Nishizuka Y. (1991) Proc Natl Acad Sci U S A. 88(12):5149-53. |
DAG acting as a Substrate in a reaction in mkp1_feedback_effects Network
| Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated.
Kd for higher order reaction are not consider. |
| | Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | 1 | PKC-act-by-DAG | mkp1_feedback_
effects
Accession No. : 4 | PKC
Pathway No. : 34 | 0.008
(uM^-1 s^-1) | 8.6348
(s^-1) | Kd(bf) = 1079.377(uM) | - | Substrate
DAG
PKC-Ca
Product
PKC-Ca-DAG
| | | Ca.PKC interaction with DAG is modeled by this reaction. Kf based on Shinomura et al PNAS 88 5149-5153 1991 and Schaechter and Benowitz 1993 J Neurosci 13(10):4361 and uses the constraining procedure referred to in the general notes for PKC. | | 2 | PKC-n-DAG | mkp1_feedback_
effects
Accession No. : 4 | PKC
Pathway No. : 34 | 0.0006
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 166.6667(uM) | - | Substrate
DAG
PKC-cytosolic
Product
PKC-DAG
| | | Binding of PKC to DAG, non-Ca dependent. Kf based on Shinomura et al PNAS 88 5149-5153 1991 Tau estimated as fast and here it is about the same time-course as the formation of DAG so it will not be rate-limiting. | | 3 | DAG-Ca-PLA2-act | mkp1_feedback_
effects
Accession No. : 4 | PLA2
Pathway No. : 36 | 0.003
(uM^-1 s^-1) | 4
(s^-1) | Kd(bf) = 1333.3333(uM) | - | Substrate
DAG
PLA2-Ca*
Product
DAG-Ca-PLA2*
| | | Synergistic activation of PLA2 by Ca and DAG. Based on Leslie and Channon 1990 BBA 1045:261 The Kd is rather large and may reflect the complications in measuring DAG. For this model it is not critical since DAG is held fixed. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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