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Enzyme List for pathway Shared_Object_mTOR_pathway (Pathway Number 1097)

 Molecule Name/
Site Name 		Km (uM) kcat (1/s)Ratio
(k2/k3)		Enzyme TypeSubstrate Product
1 Enzyme Activity:
basal

Enzyme Molecule:
40S_basal		0.250.14explicit E-S complex40S_inact
40S
2 Enzyme Activity:
basal_syn

Enzyme Molecule:
Basal_
Translation		0.0550.024explicit E-S complexAA
peptide
3 Enzyme Activity:
CaMKIII_basal

Enzyme Molecule:
S6K_basal		0.9999104explicit E-S complexCaMKIII
CaMKIII_star
4 Enzyme Activity:
camkIII_phospho

Enzyme Molecule:
S6K_thr-252		114explicit E-S complexCaMKIII
CaMKIII_star
5 Enzyme Activity:
cluster_
phospho_S6K

Enzyme Molecule:
MAPK_star		17.299814explicit E-S complexS6K
S6K_star
6 Enzyme Activity:
craf-deph

Enzyme Molecule:
PPhosphatase2A		15.656864explicit E-S complexcraf-1_star
craf-1
  See parent PPhosphatase2A for parms
7 Enzyme Activity:
craf_star_
star-deph

Enzyme Molecule:
PPhosphatase2A		15.656864explicit E-S complex
  • craf-1_star_
    star
    		• craf-1_star
      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.
    8 Enzyme Activity:
    Dephosph_
    AKTthr308

    Enzyme Molecule:
    PP2A    		4.80021.84explicit E-S complexPIP3_AKT_thr308
    		PIP3_AKT
    9 Enzyme Activity:
    dephosp_S6K

    Enzyme Molecule:
    PP2A    		8.800114explicit E-S complexS6K_thr-252
    		S6K_thr-412
    10 Enzyme Activity:
    Dephos_
    AKTser473

    Enzyme Molecule:
    PP2A    		4.81.84explicit E-S complex
  • PIP3_AKT-t308_
    s473
    		• PIP3_AKT_thr308
    11 Enzyme Activity:
    dephos_clus_S6K

    Enzyme Molecule:
    PP2A    		8.800114explicit E-S complexS6K_star
    		S6K
    12 Enzyme Activity:
    dephos_S6K

    Enzyme Molecule:
    PP2A    		8.800114explicit E-S complexS6K_thr-412
    		S6K_star
    13 Enzyme Activity:
    eEF2thr-56_
    dephospho

    Enzyme Molecule:
    PP2A    		8.80030.474explicit E-S complexeEFthr-56
    		eEF2
    14 Enzyme Activity:
    eEF2thr56_basal

    Enzyme Molecule:
    CaMKIII_basal    		2104explicit E-S complexeEF2
    		eEFthr-56
    15 Enzyme Activity:
    MAPKK-deph

    Enzyme Molecule:
    PPhosphatase2A    		15.656864explicit E-S complexMAPKK_star
    		MAPKK-ser
      See: Kyriakis et al Nature 358 pp 417-421 1992 Ahn et al Curr Op Cell Biol 4:992-999 1992 for this pathway. See parent PPhosphatase2A for parms.
    16 Enzyme Activity:
    MAPKK-deph-ser

    Enzyme Molecule:
    PPhosphatase2A    		15.656864explicit E-S complexMAPKK-ser
    		MAPKK
    17 Enzyme Activity:
    MAPK_4E-BP_
    phospho

    Enzyme Molecule:
    MAPK_star    		17.90.164explicit E-S complex
  • eIF4E-BP_thr37_
    46
  • eIF4E_4E-BP_
    t37_46_s65
    • 18 Enzyme Activity:
    MAPK_4E-BP_
    star_star

    Enzyme Molecule:
    MAPK_star    		17.90.164explicit E-S complex4E-BP_t37_46
  • 4E-BP_thr37_46_
    s65
    • 19 Enzyme Activity:
    MAPK_
    star-feedback

    Enzyme Molecule:
    MAPK_star    		25.641104explicit E-S complexcraf-1_star
  • craf-1_star_
    star
    •   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_star notes.
    20 Enzyme Activity:
    MKP1-thr-deph

    Enzyme Molecule:
    MKP-1    		744explicit E-S complexMAPK_star
    		MAPK-tyr
      See MKP1-tyr-deph
    21 Enzyme Activity:
    MKP1-tyr-deph

    Enzyme Molecule:
    MKP-1    		744explicit E-S complexMAPK-tyr
    		MAPK
      The original kinetics have been modified to obey the k2 = 4 * k3 rule, while keeping kcat and Km fixed. As noted in the NOTES, the only constraining data point is the time course of MAPK dephosphorylation, which this model satisfies. It would be nice to have more accurate estimates of rate consts and MKP-1 levels from the literature. Effective Km : 67 nM kcat = 1.43 umol/min/mg
    22 Enzyme Activity:
    phospho

    Enzyme Molecule:
    CaMKIII_CaM-Ca4    		2104explicit E-S complexeEF2
    		eEFthr-56
    23 Enzyme Activity:
    phosph_Sos

    Enzyme Molecule:
    MAPK_star    		2.5641104explicit E-S complexSos
    		Sos_star
      See Porfiri and McCormick JBC 271:10 pp5871 1996 for the existence of this step. We'll take the rates from the ones used for the phosph of Raf by MAPK. Sep 17 1997: The transient activation curve matches better with k1 up by 10 x.
    24 Enzyme Activity:
    PIP2_phospho_
    Ras-GTP

    Enzyme Molecule:
    Ras-GTP_PI3K    		444explicit E-S complexPIP2
    		PIP3
    25 Enzyme Activity:
    PIP3_dephosp

    Enzyme Molecule:
    PTEN    		0.085.54explicit E-S complexPIP3
    		PIP2
    26 Enzyme Activity:
    PKC-act-GEF

    Enzyme Molecule:
    PKC-active    		3.333344explicit E-S complexinact-GEF
    		GEF_star
      Rate consts from PKC-act-raf. This reaction activates GEF. It can lead to at least 2X stim of ras, and a 2X stim of MAPK over and above that obtained via direct phosph of c-raf. Note that it is a push-pull reaction, and there is also a contribution through the phosphorylation and inactivation of GAPs. The original PKC-act-raf rate consts are too fast. We lower K1 by 10 X
    27 Enzyme Activity:
    PKC-act-raf

    Enzyme Molecule:
    PKC-active    		20.000844explicit E-S complexcraf-1
    		craf-1_star
      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
    28 Enzyme Activity:
    PKC-inact-GAP

    Enzyme Molecule:
    PKC-active    		3.333344explicit E-S complexGAP
    		GAP_star
      Rate consts copied from PCK-act-raf This reaction inactivates GAP. The idea is from the Boguski and McCormick review.
    29 Enzyme Activity:
    PLC_g_phospho

    Enzyme Molecule:
    PLCg_basal    		0.30.54explicit E-S complexPLC_g
    		PLC_g_star
    30 Enzyme Activity:
    PP2A_4E-BP

    Enzyme Molecule:
    PP2A    		8.800314explicit E-S complex
  • eIF4E_4E-BP_
    t37_46_s65
  • eIF4E-BP_thr37_
    46
    • 31 Enzyme Activity:
    PP2A_4E-BP_star

    Enzyme Molecule:
    PP2A    		8.814explicit E-S complex4E-BP_t37_46
    		4E-BP
    32 Enzyme Activity:
    PP2A_4E-BP_
    star_star

    Enzyme Molecule:
    PP2A    		8.814explicit E-S complex
  • 4E-BP_thr37_46_
    s65
    		• 4E-BP_t37_46
    33 Enzyme Activity:
    PP2A_4EBP

    Enzyme Molecule:
    PP2A    		8.800314explicit E-S complex
  • eIF4E-BP_thr37_
    46
    		• eIF4E-BP
    34 Enzyme Activity:
    pro_syn

    Enzyme Molecule:
    Translation_clx    		0.0550.024explicit E-S complexAA
    		peptide
    35 Enzyme Activity:
    rad_basal_syn

    Enzyme Molecule:
    Basal_
    Translation    		0.0550.024explicit E-S complexrad_AA
    		peptide
    36 Enzyme Activity:
    rad_pro_syn

    Enzyme Molecule:
    Translation_clx    		0.060.024explicit E-S complexrad_AA
    		rad_peptide
    37 Enzyme Activity:
    S6K_phospho

    Enzyme Molecule:
    TOR_Rheb-GTP_
    clx    		0.80.064explicit E-S complexS6K_star
    		S6K_thr-412
    38 Enzyme Activity:
    S6K_phospho

    Enzyme Molecule:
    PDK1    		1014explicit E-S complexS6K_thr-412
    		S6K_thr-252
    39 Enzyme Activity:
    S6_phospho

    Enzyme Molecule:
    S6K_thr-252    		0.250.14explicit E-S complex40S_inact
    		40S
    40 Enzyme Activity:
    Sos.Ras_GEF

    Enzyme Molecule:
    Shc_
    star.Sos.Grb2    		0.50510.24explicit E-S complexGDP-Ras
    		GTP-Ras
    41 Enzyme Activity:
    TOR_4E-BP_
    phospho

    Enzyme Molecule:
    TOR_Rheb-GTP_
    clx    		1.814explicit E-S complexeIF4E-BP
  • eIF4E-BP_thr37_
    46
    • 42 Enzyme Activity:
    TOR_4E-BP_star

    Enzyme Molecule:
    TOR_Rheb-GTP_
    clx    		1.814explicit E-S complex4E-BP
    		4E-BP_t37_46
    43 Enzyme Activity:
    TSC2phospho

    Enzyme Molecule:
    TSC1-TSC2    		0.3204explicit E-S complexRheb-GTP
    		Rheb-GDP
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