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Molecule Parameter List for craf-1_star

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_star participated as	Molecule	Sum total of	Enzyme	Substrate of an enzyme	Product of an enzyme	Substrate in Reaction	Product in Reaction
No. of occurrences	1	0	0	2	2	1	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
mTOR_pathway	92	Network	Shared_Object_mTOR_pathway,  AKT_mod,  S6Kinase,   PI3K_mod,  TrKB_mod,  mTOR_model,   MAPK,  PKC,  4E-BP_mod,   Ras,  Sos,  43S_complex,   CaM
This model consists of various sub-modules. They are as follows: 1) BDNF receptor signaling 2) AKT signaling 3) 4E-BP model 4) S6 Kinase model 5) CaMKIII model 6) Protein synthesis model 7) CaM 8) PKC 9) MAPK model.

craf-1_star acting as a Molecule in  mTOR_pathway Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
craf-1_star	mTOR_pathway Accession No. : 92	MAPK Pathway No. : 1103	0	1000	No

craf-1_star acting as a Substrate for an Enzyme in  mTOR_pathway Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	MAPK_star  / MAPK_ star-feedback	mTOR_pathway Accession No. : 92	Shared_Object_ mTOR_pathway Pathway No. : 1097	25.641	10	4	explicit E-S complex	Substrate craf-1_star Product 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.
2	PPhosphatase2A  / craf-deph	mTOR_pathway Accession No. : 92	Shared_Object_ mTOR_pathway Pathway No. : 1097	15.6568	6	4	explicit E-S complex	Substrate craf-1_star Product craf-1
	See parent PPhosphatase2A for parms

craf-1_star acting as a Product of an Enzyme in  mTOR_pathway Network

	Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
1	PPhosphatase2A  / craf_star_ star-deph	mTOR_pathway Accession No. : 92	Shared_Object_ mTOR_pathway Pathway No. : 1097	15.6568	6	4	explicit E-S complex	Substrate craf-1_star_ star Product 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.
2	PKC-active  / PKC-act-raf	mTOR_pathway Accession No. : 92	Shared_Object_ mTOR_pathway Pathway No. : 1097	20.0008	4	4	explicit E-S complex	Substrate craf-1 Product 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

craf-1_star acting as a Substrate in a reaction in  mTOR_pathway 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.

Name	Accession Name	Pathway Name	Kf	Kb	Kd	tau	Reagents
Ras-act-craf	mTOR_pathway Accession No. : 92	Shared_Object_ mTOR_pathway Pathway No. : 1097	9.9996 (uM^-1 s^-1)	0.5 (s^-1)	Kd(bf) = 0.05(uM)	-	Substrate GTP-Ras craf-1_star Product Raf_ star-GTP-Ras
Assume the binding is fast and limited only by the amount of Ras_star 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.