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Molecule Parameter List for PLA2-cytosolic

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

PLA2-cytosolic 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	1	0	2	1

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
Synaptic_ Network	16	Network	Shared_Object_Synaptic_Network,  PKC,  PLA2,   PLCbeta,  Gq,  MAPK,   Ras,  EGFR,  Sos,   PLC_g,  CaMKII,  CaM,   PP1,  PP2B,  PKA,   AC,  CaRegulation
This model is an annotated version of the synaptic signaling network. The primary reference is Bhalla US and Iyengar R. Science (1999) 283(5400):381-7 but several of the model pathways have been updated. Bhalla US Biophys J. 2002 Aug;83(2):740-52 Bhalla US J Comput Neurosci. 2002 Jul-Aug;13(1):49-62

PLA2-cytosolic acting as a Molecule in  Synaptic_Network Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
PLA2-cytosolic	Synaptic_ Network Accession No. : 16	PLA2 Pathway No. : 72	0.4	1000	No
cPLA2 IV form has mol wt of 85 Kd. Glaser et al 1993 TIPS 14:92-98. Calculated cytosolic concentration is ~300 nM from Wijkander and Sundler 1991 Eur J Biochem 202:873 Leslie and Channon 1990 BBA 1045:261 use about 400 nM. Decent match. Use 400 nM.

PLA2-cytosolic acting as a Substrate for an Enzyme in  Synaptic_Network Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
MAPK*  / MAPK*	Synaptic_ Network Accession No. : 16	Shared_Object_ Synaptic_ Network Pathway No. : 70	25.641	20	4	explicit E-S complex	Substrate PLA2-cytosolic Product PLA2*
Km = 25uM @ 50 uM ATP and 1mg/ml MBP (huge XS of substrate) Vmax = 4124 pmol/min/ml at a conc of 125 pmol/ml of enz. Numbers are from Sanghera et al JBC 265 pp 52 , 1990. From Nemenoff et al 1993 JBC 268(3):1960-1964 - using Sanghera's 1e-4 ratio of MAPK to protein, we get k3 = 7/sec from 1000 pmol/min/mg total protein in fig 5 I take the Vmax to be higher for PLA2 given the fold activation of PLA2 by MAPK. This is actually a balance term between MAPK and the dephosphorylation step.

PLA2-cytosolic acting as a Substrate in a reaction in  Synaptic_Network 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
1	PLA2-Ca-act	Synaptic_ Network Accession No. : 16	PLA2 Pathway No. : 72	1 (uM^-1 s^-1)	0.1 (s^-1)	Kd(bf) = 0.1(uM)	-	Substrate Ca PLA2-cytosolic Product PLA2-Ca*
	Direct activation of PLA2 by Ca. From Leslie and Channon BBA 1045 (1990) 261-270 fig6 pp267.
2	PIP2-PLA2-act	Synaptic_ Network Accession No. : 16	PLA2 Pathway No. : 72	0.0012 (uM^-1 s^-1)	0.5 (s^-1)	Kd(bf) = 416.6667(uM)	-	Substrate PLA2-cytosolic temp-PIP2 Product PIP2-PLA2*
	Activation of PLA2 by PIP2. From Leslie and Channon 1990 BBA 1045:261 the stimulation of PLA2 activity by high PIP2 is 7x. In this model we don't really expect any PIP2 stimulus.

PLA2-cytosolic acting as a Product in a reaction in  Synaptic_Network 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
dephosphorylate- PLA2*	Synaptic_ Network Accession No. : 16	PLA2 Pathway No. : 72	0.17 (s^-1)	0 (s^-1)	-	-	Substrate PLA2* Product PLA2-cytosolic
Dephosphorylation reaction to balance MAPK phosphorylation of PLA2. This is probably mediated by PP2A. Rates determined to keep the balance of phosphorylated and non-phosphorylated PLA2 reasonable. The constraining factor is the fold activation of PLA2 by MAPK.