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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
  • MAPK_network_
    2003
  • 50Network
    Shared_Object_MAPK_network_2003 PKC PLA2 
    PLCbeta Gq MAPK 
    Ras EGFR Sos 
    PLC_g CaMKII CaM 
    PP1 PP2B PKA 
    AC 
    This is a network model of many pathways present at the neuronal synapse. The network has properties of temporal tuning as well as steady-state computational properties. In its default form the network is bistable.Bhalla US Biophys J. 2004 Aug;87(2):745-53

    craf-1* acting as a Molecule in  
    MAPK_network_2003 Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    craf-1*
  • MAPK_network_
    2003

    Accession No. : 50
  • MAPK
    Pathway No. : 211
    01000No

    craf-1* acting as a Substrate for an Enzyme in  
    MAPK_network_2003 Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1MAPK*  /
    MAPK*-feedback
  • MAPK_network_
    2003

    Accession No. : 50
  • Shared_Object_
    MAPK_network_
    2003

    Pathway No. : 206
  • 25.641104explicit 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
  • MAPK_network_
    2003

    Accession No. : 50
  • Shared_Object_
    MAPK_network_
    2003

    Pathway No. : 206
  • 15.656664.16667explicit E-S complexSubstrate
    craf-1*

    Product
    craf-1
        See parent PPhosphatase2A for parms

    craf-1* acting as a Product of an Enzyme in  
    MAPK_network_2003 Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1PKC-active  /
    PKC-act-raf
  • MAPK_network_
    2003

    Accession No. : 50
  • Shared_Object_
    MAPK_network_
    2003

    Pathway No. : 206
  • 66.666744explicit 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
  • MAPK_network_
    2003

    Accession No. : 50
  • Shared_Object_
    MAPK_network_
    2003

    Pathway No. : 206
  • 15.656664.16667explicit 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  
    MAPK_network_2003 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
  • MAPK_network_
    2003

    Accession No. : 50
  • Shared_Object_
    MAPK_network_
    2003

    Pathway No. : 206
  • 24
    (uM^-1 s^-1)
    0.5
    (s^-1)
    Kd(bf) = 0.0208(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 (I don't....



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