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Molecule List for Accession CaMKII_2003 (Accession Number49)

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The entries are grouped according to Pathway Number and are alternately color coded using  and  color.
  NamePathway Name / 
Pathway No.
Accession
Type
Initial
Conc.

(uM)
Volume
(fL)
BufferedSum Total Of
1 CaMKII CaMKII

Pathway No. 202
Network701000No
    Huge conc of CaMKII. In PSD it is 20-40% of protein, so we assume it is around 2.5% of protein in spine as a whole. This level is so high it is unlikely to matter much if we are off a bit. This comes to about 70 uM.
2 CaM CaM

Pathway No. 203
Network201000No
    There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al) Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying it is comparable to CaMK levels.
3 neurogranin CaM

Pathway No. 203
Network101000No
    Also known as RC3 and p17 and BICKS. Conc in brain >> 2 uM from Martzen and Slemmon J neurosci 64 92-100 1995 but others say less without any #s. Conc in dend spines is much higher than overall, so it could be anywhere from 2 uM to 50. We will estimate 10 uM as a starting point. Gerendasy et al JBC 269:35 22420-22426 1994 have a skeleton model (no numbers) indicating CaM-Ca(n) binding ....
4 PP1-active
  • Shared_Object_
    CaMKII_2003

    Pathway No. 201
  • Network1.81000No
        Cohen et al Meth Enz 159 390-408 is main source of info conc = 1.8 uM
    5 I1 PP1

    Pathway No. 204
    Network1.81000No
        I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need >= 1.8 uM.
    6 CaNAB PP2B

    Pathway No. 205
    Network11000No
        We assume that the A and B subunits of PP2B are always bound under physiol conditions. Up to 1% of brain protein = 25 uM. I need to work out how it is distributed between cytosolic and particulate fractions. Tallant and Cheung '83 Biochem 22 3630-3635 have conc in many species, average for mammalian brain is around 1 uM.
    7 PP2A
  • Shared_Object_
    CaMKII_2003

    Pathway No. 201
  • Network0.121000No
    8 PKC-active
  • Shared_Object_
    CaMKII_2003

    Pathway No. 201
  • Network0.091000Yes
    9 Ca
  • Shared_Object_
    CaMKII_2003

    Pathway No. 201
  • Network0.081000Yes
    10 PKA-active
  • Shared_Object_
    CaMKII_2003

    Pathway No. 201
  • Network0.0151000Yes
    11 I1* PP1

    Pathway No. 204
    Network0.0011000No
        Dephosph is mainly by PP2B
    12 CaM-Ca4
  • Shared_Object_
    CaMKII_2003

    Pathway No. 201
  • Network01000No
    13 CaMKII-CaM CaMKII

    Pathway No. 202
    Network01000No
    14 
  • CaMKII-thr286*-C
    aM
  •  CaMKII

    Pathway No. 202
    Network01000No
        From Hanson and Schulman, the thr286 is responsible for autonomous activation of CaMKII.
    15 CaMKII*** CaMKII

    Pathway No. 202
    Network01000No
        From Hanson and Schulman, the CaMKII does a lot of autophosphorylation just after the CaM is released. This prevents further CaM binding and renders the enzyme quite independent of Ca.
    16 CaMKII-thr286 CaMKII

    Pathway No. 202
    Network01000No
        I am not sure if we need to endow this one with a lot of enzs. It is likely to be a short-lived intermediate, since it will be phosphorylated further as soon as the CAM falls off.
    17 CaMK-thr306 CaMKII

    Pathway No. 202
    Network01000No
        This forms due to basal autophosphorylation, but I think it has to be considered as a pathway even if some CaM is floating around. In either case it will tend to block further binding of CaM, and will not display any enzyme activity. See Hanson and Schulman JBC 267:24 pp17216-17224 1992
    18 neurogranin-CaM CaM

    Pathway No. 203
    Network01000No
    19 neurogranin* CaM

    Pathway No. 203
    Network01000No
        The phosph form does not bind CaM (Huang et al ABB 305:2 570-580 1993)
    20 CaM-Ca3
  • Shared_Object_
    CaMKII_2003

    Pathway No. 201
  • Network01000No

     
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