cascade - mapk rule-based)
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1 cacade - mapk rule-baed) Thurday, 5 November 2009
2 !tline - tart with a baic motive of reverible covalent modification - obtain a rule-baed verion of the Huang-Ferell model of a protein activation cacade [2] - and finally, rewire our cacade to illutrate how eay it i to do o Thurday, 5 November 2009
3 GK-loop three type of agent: - a kinae K, - a target T with 2 pho ite and y, and - a phophatae P elementary triplet: - K bind it target T at ite or y, - K may (but need not) phophorylate the ite to which it i bound, - K diociate from T Thurday, 5 November 2009
4 KPT - rule K(a), T() K(a 1 ), T( 1 ) K(a 1 ), T( 1 u) K(a 1 ), T( 1 p) K(a), T(y) K(a 1 ), T(y 1 ) K(a 1 ), T(yu) 1 K(a 1 ), T(yp) 1 P(a), T() P(a 1 ), T( 1 ) P(a 1 ), T( 1 p) P(a 1 ), T( 1 u) P(a), T(y) P(a 1 ), T(y 1 ) P(a 1 ), T(yp) 1 P(a 1 ), T(yu) 1 i a recurrent motif with man Thurday, 5 November 2009
5 typology of GK variation on multi-pho ytem: - proceive v. ditributive - mart = ~U, ~P enitive v. dumb - equential v. unordered - ecluive v. collective Thurday, 5 November 2009
6 3 GK in equence 3 tier: - Ra -> <- - -> <- - -> <- RAS(), RAF( u ) RAS( 1 ), RAF( 1 u) RAS( 1 ), RAF( 1 u) RAS( 1 ), RAF( 1 p) RAS( 1 ), RAF( 1 ) RAS(), RAF() 85~p!1) 87~p!1) of by : (), RAF( p ) ( 1 ), RAF( 1 p) ( 1 ), RAF( 1 p) ( 1 ), RAF( 1 u) ( 1 ), RAF( 1 ) (), RAF() Ra Thurday, 5 November 2009
7 3 GK - tier 2 RAF( p ), ( u ) RAF( 1 p), ( 1 u) RAF( 1 p), ( 1 u) RAF( 1 p), ( 1 p) RAF( 1 p), ( 1 ) RAF( p ), () RAF( p ), ( u ) RAF( 1 p), ( 1 u) RAF( 1 p), ( 1 u) RAF( 1 p), ( 1 p) RAF( 1 p), ( 1 ) RAF( p ), () (), ( p ) ( 1 ), ( 1 p) ( 1 ), ( 1 p) ( 1 ), ( 1 u) ( 1 ), ( 1 ) (), () (), ( p ) ( 1 ), ( 1 p) ( 1 ), ( 1 p) ( 1 ), ( 1 u) ( 1 ), ( 1 ) (), () 85~p!1) 87~p!1) Ra Thurday, 5 November 2009
8 3 GK - tier 3 (, p, p ), ( u ) ( 1, p, p ), ( 1 u) ( 1, p, p ), ( 1 u) ( 1, p, p ), ( 1 p) ( 1, p, p ), ( 1 ) (, p, p ), () (, p, p ), ( u ) ( 1, p, p ), ( 1 u) ( 1, p, p ), ( 1 u) ( 1, p, p ), ( 1 p) ( 1, p, p ), ( 1 ) (, p, p ), () (), ( p ) ( 1 ), ( 1 p) ( 1 ), ( 1 p) ( 1 ), ( 1 u) ( 1 ), ( 1 ) (), () (), ( p ) ( 1 ), ( 1 p) ( 1 ), ( 1 p) ( 1 ), ( 1 u) ( 1 ), ( 1 ) (), () 85~p!1) 87~p!1) Ra Thurday, 5 November 2009
9 imulation Ra(~gtp),(~u) -> Ra(~gtp!1),( Ra(~gtp!1),(~u!1) -> Ra(~gtp!1),(~p!1) Ra(~gtp!1),(!1) -> Ra(~gtp),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() (~p),(~u) -> (~p!1),( (~p!1),(~u!1) -> (~p!1),(~p!1) (~p!1),(!1) -> (~p),() (~p),(~u) -> (~p!1),( (~p!1),(~u!1) -> (~p!1),(~p!1) (~p!1),(!1) -> (~p),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() (,~p,~p),(~u) -> (!1,~p,~p),( (!1,~p,~p),(~u!1) -> (!1,~p,~p),(~p!1) (!1,~p,~p),(!1) -> (,~p,~p),() (,~p,~p),(~u) -> (!1,~p,~p),( (!1,~p,~p),(~u!1) -> (!1,~p,~p),(~p!1) (!1,~p,~p),(!1) -> (,~p,~p),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() Ra Thurday, 5 November 2009
10 rewi#ng!r GK*3 RAF( p ), () RAF( 1 p), ( 1 ) RAF( 1 p), ( 1 ) RAF( p ), () RAF( 1 p), ( u, 1 ) RAF( 1 p), ( p, 1 ) RAF( 1 p), ( u, 1 ) RAF( 1 p), ( p, 1 ) the modification, the cacade no longer activate 85~p!1) 87~p!1) 85 (~p!1) 5) 87 (~p!1) 7) Ra Ra Thurday, 5 November 2009
11 imulation - rewired Ra(~gtp),(~u) -> Ra(~gtp!1),( Ra(~gtp!1),(~u!1) -> Ra(~gtp!1),(~p!1) _op' Ra(~gtp!1),(!1) -> Ra(~gtp),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() (~p),() -> (~p!1),(!1) (~p!1),(!1) -> (~p),() (~p!1),(~u,!1) -> (~p!1),(~p,!1) (~p!1),(~u,!1) -> (~p!1),(~p,!1) # (~p),(~u) -> (~p!1),( # (~p!1),(~u!1) -> (~p!1),(~p!1) # (~p!1),(!1) -> (~p),() # (~p),(~u) -> (~p!1),( # (~p!1),(~u!1) -> (~p!1),(~p!1) # (~p!1),(!1) -> (~p),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() (,~p,~p),(~u) -> (!1,~p,~p),( (!1,~p,~p),(~u!1) -> (!1,~p,~p),(~p!1) (!1,~p,~p),(!1) -> (,~p,~p),() (,~p,~p),(~u) -> (!1,~p,~p),( (!1,~p,~p),(~u!1) -> (!1,~p,~p),(~p!1) (!1,~p,~p),(!1) -> (,~p,~p),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() (),(~p) -> (!1),(~p!1) (!1),(~p!1) -> (!1),( (!1),(!1) -> (),() Ra the cacade no longer work - why? Thurday, 5 November 2009
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