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Molecule Parameter List for L.EGFR

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

L.EGFR 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	1	0	0	1	1

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
EGFR_MAPK	58	Network	Shared_Object_EGFR_MAPK,  MAPK,  Ras,   EGFR,  Sos
Model of MAPK activation by EGFR in the synapse. Demonstration programs using this model are available here. Primary citation:Bhalla US. Biophys J. (2004) 87(2):745-53.

L.EGFR acting as a Molecule in  EGFR_MAPK Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
L.EGFR	EGFR_MAPK Accession No. : 58	EGFR Pathway No. : 232	0	1000	No
This is terribly simplified: there are many interesting intermediate stages, including dimerization and assoc with adapter molecules like Shc, that contribute to the activation of the EGFR.

L.EGFR acting as an Enzyme in  EGFR_MAPK Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
L.EGFR / phosph_Shc	EGFR_MAPK Accession No. : 58	EGFR Pathway No. : 232	0.833333	0.2	4	explicit E-S complex	Substrate SHC Product SHC*
Rates from Okada et al JBC 270:35 pp 20737 1995 Km = 0.70 to 0.85 uM, Vmax = 4.4 to 5.0 pmol/min. Unfortunately the amount of enzyme is not known, the prep is only partially purified. Time course of phosph is max within 30 sec, falls back within 20 min. Ref: Sasaoka et al JBC 269:51 32621 1994. Use k3 = 0.1 based on this tau.

L.EGFR acting as a Substrate in a reaction in  EGFR_MAPK 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
Internalize	EGFR_MAPK Accession No. : 58	EGFR Pathway No. : 232	0.002 (s^-1)	0.0003 (s^-1)	Keq = 0.165(uM)	434.783sec	Substrate L.EGFR Product Internal_L.EGFR
See Helin and Beguinot JBC 266:13 1991 pg 8363-8368. In Fig 3 they have internalization tau about 10 min, equil at about 20% EGF available. So kf = 4x kb, and 1/(kf + kb) = 600 sec so kb = 1/3K = 3.3e-4, and kf = 1.33e-3. This doesn't take into account the unbound receptor, so we need to push the kf up a bit, to 0.002

L.EGFR acting as a Product in a reaction in  EGFR_MAPK 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
act_EGFR	EGFR_MAPK Accession No. : 58	EGFR Pathway No. : 232	4.2 (uM^-1 s^-1)	0.25 (s^-1)	Kd(bf) = 0.0595(uM)	-	Substrate EGF EGFR Product L.EGFR
Affinity of EGFR for EGF is complex: depends on [EGFR]. We'll assume fixed [EGFR] and use exptal affinity ~20 nM (see Sherrill and Kyte Biochem 1996 35 5705-5718, Berkers et al JBC 266:2 922-927 1991, Sorokin et al JBC 269:13 9752-9759 1994). Tau =~2 min (Davis et al JBC 263:11 5373-5379 1988) or Berkers Kass = 6.2e5/M/sec, Kdiss=3.5e-4/sec. Sherrill and Kyte have Hill Coeff=1.7