MODEL1006230001
type: SBMLModel
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
units def: 204819
units def: 205036
units def: 205011
parameter: 630299
parameter: 630288
parameter: 630296
rule: 630265
parameter: 630300
rule: 630271
created:
  W3 CDTF: Fri Jun 25 13:00:33 BST 2010
rule: 630263
parameter: 630281
parameter: 630287
parameter: 630294
parameter: 630285
parameter: 630305
volume units: 950046
units def: 205072
rule: 630272
parameter: 630278
is described by: http://identifiers.org/pubmed/11027188
parameter: 630297
notes: This a model from the article: Computational model for effects of ligand/receptor binding properties on interleukin-2 trafficking dynamics and T cell proliferation response. Fallon EM, Lauffenburger DA. Biotechnol Prog 2000 Sep-Oct;16(5):905-16 11027188 , Abstract: Multisubunit cytokine receptors such as the heterotrimeric receptor for interleukin-2 (IL-2) are ubiquitous in hematopoeitic cell types of importance in biotechnology and are crucial regulators of cell proliferation and differentiation behavior. Dynamics of cytokine/receptor endocytic trafficking can significantly impact cell responses through effects of receptor down-regulation and ligand depletion, and in turn are governed by ligand/receptor binding properties. We describe here a computational model for trafficking dynamics of the IL-2 receptor (IL-2R) system, which is able to predict T cell proliferation responses to IL-2. This model comprises kinetic equations describing binding, internalization, and postendocytic sorting of IL-2 and IL-2R, including an experimentally derived dependence of cell proliferation rate on these properties. Computational results from this model predict that IL-2 depletion can be reduced by decreasing its binding affinity for the IL-2R betagamma subunit relative to the alpha subunit at endosomal pH, as a result of enhanced ligand sorting to recycling vis-a-vis degradation, and that an IL-2 analogue with such altered binding properties should exhibit increased potency for stimulating the T cell proliferation response. These results are in agreement with our recent experimental findings for the IL-2 analogue termed 2D1 [Fallon, E. M. et al. J. Biol. Chem. 2000, 275, 6790-6797]. Thus, this type of model may enable prediction of beneficial cytokine/receptor binding properties to aid development of molecular design criteria for improvements in applications such as in vivo cytokine therapies and in vitro hematopoietic cell bioreactors. This model was taken from the CellML repositor…
name: Fallon2000_IL2dynamics
rule: 630270
compartment: 630254
rule: 630266
parameter: 630303
units def: 204891
parameter: 630302
parameter: 630308
units def: 204963
modified:
  W3 CDTF: Fri Jun 25 13:00:33 BST 2010
parameter: 630280
substance units: 178797
parameter: 630293
parameter: 630284
length unit: 335510
rule: 630273
units def: 205096
rule: 630269
area units: area
units def: 204987
rule: 630264
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
rule: 630275
time units: 205096
parameter: 630291
parameter: 630282
curated: false
parameter: 630290
rule: 630262
units def: 204915
units def: 204783
units def: 204843
modified:
  W3 CDTF: Fri Jun 25 13:00:33 BST 2010
modified:
  W3 CDTF: Fri Jun 25 13:00:33 BST 2010
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
parameter: 630306
parameter: 630279

204819
type: SBMLUnitsDef
unit: 204831
name: minute

204831
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 60.0
kind: SECOND

205036
type: SBMLUnitsDef
unit: 205060
unit: 205048
name: cell_per_L_minute

205060
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND

205048
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

205011
type: SBMLUnitsDef
unit: 205023
name: L_per_cell

205023
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

630299
type: Parameter
constant: true
units: 204891
value: 0.0011
name: ksyn

204891
type: SBMLUnitsDef
unit: 204903
name: first_order_rate_constant

204903
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND

630288
type: Parameter
constant: false
units: 205072
value: 2.5E8
name: Y

205072
type: SBMLUnitsDef
unit: 205084
name: cell_per_L

205084
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

630296
type: Parameter
constant: true
units: 204891
value: 0.007
name: kt

630300
type: Parameter
constant: true
units: 204891
value: 0.04
name: ke

630281
type: Parameter
constant: false
value: 300.0
name: Ri

630287
type: Parameter
constant: false
units: 204783
value: 10.0
name: L

204783
type: SBMLUnitsDef
unit: 204807
unit: 204795
name: picomolar

204807
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

204795
type: SBMLUnit
exponent: 1.0
scale: -12
multipler: 1.0
kind: MOLE

630294
type: Parameter
constant: false
units: 204915
value: NaN
name: kfe

204915
type: SBMLUnitsDef
unit: 204951
unit: 204939
unit: 204927
name: second_order_rate_constant

204951
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND

204939
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

204927
type: SBMLUnit
exponent: -1.0
scale: -12
multipler: 1.0
kind: MOLE

630285
type: Parameter
constant: false
value: 1.0
name: Ld

630305
type: Parameter
constant: true
units: 205011
value: 1.0E-14
name: Ve

630278
type: Parameter
constant: true
units: 204819
value: NaN
name: time

630297
type: Parameter
constant: true
units: 204987
value: 11.0
name: Vs

204987
type: SBMLUnitsDef
unit: 204999
name: number_per_cell_minute

204999
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND

630254
type: Compartment
constant: true
units: litre
size: 1.0
spatial dimensions: 3.0

630303
type: Parameter
constant: true
units: 204891
value: 0.035
name: kh

630302
type: Parameter
constant: true
units: 204891
value: 0.15
name: kx

630308
type: Parameter
constant: true
units: dimensionless
value: 1.0
name: IL2

204963
type: SBMLUnitsDef
unit: 204975
name: number_per_picomole

204975
type: SBMLUnit
exponent: -1.0
scale: -12
multipler: 1.0
kind: MOLE

630280
type: Parameter
constant: false
value: 1.0
name: Cs

630293
type: Parameter
constant: false
units: 204891
value: NaN
name: kre

630284
type: Parameter
constant: false
value: 0.01
name: Li

205096
type: SBMLUnitsDef
unit: 205108
name: time

205108
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 60.0
kind: SECOND

630291
type: Parameter
constant: false
units: 204915
value: NaN
name: kf

630282
type: Parameter
constant: false
value: 1.0
name: Ci

630290
type: Parameter
constant: true
units: 204891
value: 0.0138
name: kr

204843
type: SBMLUnitsDef
unit: 204879
unit: 204867
unit: 204855
name: flux

204879
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND

204867
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

204855
type: SBMLUnit
exponent: 1.0
scale: -12
multipler: 1.0
kind: MOLE

630306
type: Parameter
constant: true
units: 204963
value: 6.022E11
name: NA

630279
type: Parameter
constant: false
value: 1500.0
name: Rs