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Molecule Parameter List for craf-1*

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
craf-1* participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1002210

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • Ajay_Bhalla_
    2007_Bistable
  • 79Network
    Shared_Object_Ajay_Bhalla_2007_Bistable PKC PLA2 
    MAPK Ras CaM 
    This is a model of ERKII signaling which is bistable due to feedback. The feedback occurs through ERKII phosphorylation of phospholipase A2 (PLA2), leading to increased production of arachidonic acid (AA), which activates protein kinase C (PKC) which activates c-Raf which is upstream of ERKII.
    The model is a highly simplified variant of more detailed bistable models of MAPK signaling (Bhalla US, Iyengar R. Science. 1999 Jan 15;283(5400):381-7, Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80)

    craf-1* acting as a Molecule in  
    Ajay_Bhalla_2007_Bistable Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    craf-1*
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • MAPK
    Pathway No. : 366
    0125.7No

    craf-1* acting as a Substrate for an Enzyme in  
    Ajay_Bhalla_2007_Bistable Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1MAPK*  /
    MAPK*-feedback
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Shared_Object_
    Ajay_Bhalla_
    2007_Bistable

    Pathway No. : 363
  • 25.6402104explicit E-S complexSubstrate
    craf-1*

    Product
    craf-1**
        Ueki et al JBC 269(22):15756-15761 show the presence of this step, but not the rate consts, which are derived from Sanghera et al JBC 265(1):52-57, 1990, see the deriv in the MAPK* notes.
    2PPhosphatase2A  /
    craf-deph
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Shared_Object_
    Ajay_Bhalla_
    2007_Bistable

    Pathway No. : 363
  • 15.656664explicit E-S complexSubstrate
    craf-1*

    Product
    craf-1
        See parent PPhosphatase2A for parms

    craf-1* acting as a Product of an Enzyme in  
    Ajay_Bhalla_2007_Bistable Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1PKC-active  /
    PKC-act-raf
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Shared_Object_
    Ajay_Bhalla_
    2007_Bistable

    Pathway No. : 363
  • 66.667144explicit E-S complexSubstrate
    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
    2PPhosphatase2A  /
    craf**-deph
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Shared_Object_
    Ajay_Bhalla_
    2007_Bistable

    Pathway No. : 363
  • 15.656664explicit E-S complexSubstrate
    craf-1**

    Product
    craf-1*
        Ueki et al JBC 269(22) pp 15756-15761 1994 show hyperphosphorylation of craf, so this is there to dephosphorylate it. Identity of phosphatase is not known to me, but it may be PP2A like the rest, so I have made it so.

    craf-1* acting as a Substrate in a reaction in  
    Ajay_Bhalla_2007_Bistable 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.
    NameAccession NamePathway NameKfKbKdtauReagents
    Ras-act-craf
  • Ajay_Bhalla_
    2007_Bistable

    Accession No. : 79
  • Shared_Object_
    Ajay_Bhalla_
    2007_Bistable

    Pathway No. : 363
  • 9.9999
    (uM^-1 s^-1)
    0.5
    (s^-1)
    Kd(bf) = 0.05(uM)-Substrate
    GTP-Ras
    craf-1*

    Product
    Raf*-GTP-Ras
    Assume the binding is fast and limited only by the amount of Ras* available. So kf=kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So we raise kb 4x to 4 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414 May 16, 2003 Changed Ras and Raf to synaptic levels, an increase of about 2x for each. To maintain the percentage of complexed Raf, reduced the kf by 2.4 fold to 10.



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