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Molecule Parameter List for MAPK-tyr

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
MAPK-tyr participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1004400

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • mkp1_feedback_
    effects
  • 4Network
    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.

    MAPK-tyr acting as a Molecule in  
    mkp1_feedback_effects Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    MAPK-tyr
  • mkp1_feedback_
    effects

    Accession No. : 4
  • MAPK
    Pathway No. : 35
    01000No
    Haystead et al FEBS Lett. 306(1) pp 17-22 show that phosphorylation is strictly sequential, first tyr185 then thr183.

    MAPK-tyr acting as a Substrate for an Enzyme in  
    mkp1_feedback_effects Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1MAPKK*  /
    MAPKKthr
  • mkp1_feedback_
    effects

    Accession No. : 4
  • MAPK
    Pathway No. : 35
    0.04629630.154explicit E-S complexSubstrate
    MAPK-tyr

    Product
    MAPK*
        Rate consts same as for MAPKKtyr.
    2MKP-1**  /
    MKP1*-tyr-deph
  • mkp1_feedback_
    effects

    Accession No. : 4
  • MAPK
    Pathway No. : 35
    0.066666714Classical Michaelis-Menten
    V = Etot.S.Kcat/Km+S
    Substrate
    MAPK-tyr

    Product
    MAPK
        3 Feb 2000. Same rates as MKP-1.
    3MKP-1  /
    MKP1-tyr-deph
  • mkp1_feedback_
    effects

    Accession No. : 4
  • Shared_Object_
    mkp1_feedback_
    effects

    Pathway No. : 32
  • 0.066666714Classical Michaelis-Menten
    V = Etot.S.Kcat/Km+S
    Substrate
    MAPK-tyr

    Product
    MAPK
        The original kinetics from Bhalla US and Iyengar R. (1999) Science 283(5400):381-387 have now been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. The main constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. See Charles CH, Sun H, Lau LF, Tonks NK. (1993) Proc Natl Acad Sci U S A. 90(11):5292-5296 and Charles CH, Abler AS, Lau LF. (1992) Oncogene 7(1):187-190. Effective Km : 67 nM kcat = 1.43 umol/min/mg.
    4MKP-2  /
    MKP2-tyr-deph
  • mkp1_feedback_
    effects

    Accession No. : 4
  • Shared_Object_
    mkp1_feedback_
    effects

    Pathway No. : 32
  • 0.066666714explicit E-S complexSubstrate
    MAPK-tyr

    Product
    MAPK
        22 Apr 2001: Based on MKP1 parameters. The original kinetics have been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. The only constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. The rates are treated as the same as for MKP-1, based on Chu Y, Solski PA, Khosravi-Far R, Der CJ, Kelly K. (1996) J Biol Chem. 271(11):6497-6501.

    MAPK-tyr acting as a Product of an Enzyme in  
    mkp1_feedback_effects Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1MAPKK*  /
    MAPKKtyr
  • mkp1_feedback_
    effects

    Accession No. : 4
  • MAPK
    Pathway No. : 35
    0.04629630.154explicit E-S complexSubstrate
    MAPK

    Product
    MAPK-tyr
        The actual MAPKK is 2 forms from Seger et al JBC 267:20 14373(1992) Vmax = 150nmol/min/mg From Haystead et al FEBS 306(1):17-22 we get Km=46.6nM for at least one of the phosphs. Putting these together: k3=0.15/sec, ratio of 4 to get k2=0.6. k1=0.75/46.6nM=2.7e-5 In terms of Michaelis-Menten rates, Km = 0.046, Vmax = 0.15, ratio = 4.
    2MKP-1**  /
    MKP1*-thr-deph
  • mkp1_feedback_
    effects

    Accession No. : 4
  • MAPK
    Pathway No. : 35
    0.066666714Classical Michaelis-Menten
    V = Etot.S.Kcat/Km+S
    Substrate
    MAPK*

    Product
    MAPK-tyr
        3 Feb 2000. Same rates as MKP1
    3MKP-1  /
    MKP1-thr-deph
  • mkp1_feedback_
    effects

    Accession No. : 4
  • Shared_Object_
    mkp1_feedback_
    effects

    Pathway No. : 32
  • 0.066666714Classical Michaelis-Menten
    V = Etot.S.Kcat/Km+S
    Substrate
    MAPK*

    Product
    MAPK-tyr
        See MKP1-tyr-deph
    4MKP-2  /
    MKP2-thr-deph
  • mkp1_feedback_
    effects

    Accession No. : 4
  • Shared_Object_
    mkp1_feedback_
    effects

    Pathway No. : 32
  • 0.066666714explicit E-S complexSubstrate
    MAPK*

    Product
    MAPK-tyr
        See MKP2-tyr-deph



    Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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