// DOQCS :http://doqcs.ncbs.res.in/ // Accession Name = PKA_2003 // Accession Number = 47 // Pathway Name = PKA // Pathway Number = 196 // Transcriber = Upinder S. Bhalla, NCBS // Developer = Upinder S. Bhalla, NCBS // Species = Generic mammalian // Tissue = Generic // Cell Compartment = Cytosol + Cell membrane // Notes = General ref: Taylor et al Ann Rev Biochem 1990 59:971-1005 //genesis // kkit Version 11 flat dumpfile // Saved on Tue Dec 13 11:11:57 2005 include kkit {argv 1} FASTDT = 0.001 SIMDT = 0.001 CONTROLDT = 1 PLOTDT = 1 MAXTIME = 1000 TRANSIENT_TIME = 2 VARIABLE_DT_FLAG = 0 DEFAULT_VOL = 1.6667e-21 VERSION = 11.0 setfield /file/modpath value /home2/bhalla/scripts/modules kparms //genesis initdump -version 3 -ignoreorphans 1 simobjdump doqcsinfo filename accessname accesstype transcriber developer \ citation species tissue cellcompartment methodology sources \ model_implementation model_validation x y z simobjdump table input output alloced step_mode stepsize x y z simobjdump xtree path script namemode sizescale simobjdump xcoredraw xmin xmax ymin ymax simobjdump xtext editable simobjdump xgraph xmin xmax ymin ymax overlay simobjdump xplot pixflags script fg ysquish do_slope wy simobjdump group xtree_fg_req xtree_textfg_req plotfield expanded movealone \ link savename file version md5sum mod_save_flag x y z simobjdump geometry size dim shape outside xtree_fg_req xtree_textfg_req x y \ z simobjdump kpool DiffConst CoInit Co n nInit mwt nMin vol slave_enable \ geomname xtree_fg_req xtree_textfg_req x y z simobjdump kreac kf kb notes xtree_fg_req xtree_textfg_req x y z simobjdump kenz CoComplexInit CoComplex nComplexInit nComplex vol k1 k2 k3 \ keepconc usecomplex notes xtree_fg_req xtree_textfg_req link x y z simobjdump stim level1 width1 delay1 level2 width2 delay2 baselevel trig_time \ trig_mode notes xtree_fg_req xtree_textfg_req is_running x y z simobjdump xtab input output alloced step_mode stepsize notes editfunc \ xtree_fg_req xtree_textfg_req baselevel last_x last_y is_running x y z simobjdump kchan perm gmax Vm is_active use_nernst notes xtree_fg_req \ xtree_textfg_req x y z simobjdump transport input output alloced step_mode stepsize dt delay clock \ kf xtree_fg_req xtree_textfg_req x y z simobjdump proto x y z simundump geometry /kinetics/geometry 0 1e-15 3 sphere "" white black -1 -13 \ 0 simundump group /kinetics/PKA 0 blue blue x 0 0 "" defaultfile defaultfile.g \ 0 0 0 -11.636 -12.25 0 simundump kpool /kinetics/PKA/R2C2 0 0 0.5 0.5 3e+05 3e+05 0 0 6e+05 0 \ /kinetics/geometry white blue -16.348 -19.323 0 simundump kreac /kinetics/PKA/cAMP-bind-site-B1 0 9e-05 33 "" white blue \ -13.972 -22.598 0 simundump kreac /kinetics/PKA/cAMP-bind-site-B2 1 9e-05 33 "" white blue \ -11.63 -21.35 0 simundump kreac /kinetics/PKA/cAMP-bind-site-A1 1 0.000125 110 "" white blue \ -8.9437 -22.535 0 simundump kreac /kinetics/PKA/cAMP-bind-site-A2 1 0.000125 32.5 "" white blue \ -5.6565 -21.104 0 simundump kreac /kinetics/PKA/Release-C1 1 60 3e-05 "" white blue -5.0539 \ -14.46 0 simundump kreac /kinetics/PKA/Release-C2 1 60 3e-05 "" white blue -9.9249 \ -15.738 0 simundump kpool /kinetics/PKA/PKA-inhibitor 1 0 0.25 0.25 1.5e+05 1.5e+05 0 0 \ 6e+05 0 /kinetics/geometry cyan blue -14.407 -14.871 0 simundump kreac /kinetics/PKA/inhib-PKA 1 1e-04 1 "" white blue -11.613 \ -14.248 0 simundump kpool /kinetics/PKA/inhibited-PKA 1 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry cyan blue -15.034 -13.272 0 simundump kpool /kinetics/PKA/cAMP.R2C2 0 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry white blue -13.387 -18.855 0 simundump kpool /kinetics/PKA/cAMP2.R2C2 1 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry white blue -9.8392 -18.013 0 simundump kpool /kinetics/PKA/cAMP3.R2C2 1 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry white blue -7.1529 -19.073 0 simundump kpool /kinetics/PKA/cAMP4.R2C2 1 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry white blue -4.7663 -17.462 0 simundump kpool /kinetics/PKA/cAMP4.R2C 1 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry white blue -7.0495 -16.328 0 simundump kpool /kinetics/PKA/cAMP4.R2 1 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry white blue -13.387 -16.765 0 simundump kpool /kinetics/cAMP 1 0 0 0 0 0 0 0 6e+05 2 /kinetics/geometry \ green black -5.3828 -25.006 0 simundump kpool /kinetics/PKA-active 0 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry yellow black -7.2906 -13.501 0 simundump doqcsinfo /kinetics/doqcsinfo 0 pdb196.g PKA pathway \ "Upinder S. Bhalla, NCBS" "Upinder S. Bhalla, NCBS" "citation here" \ "Generic Mammalian" Generic "Cytosol+Cell membrane" Qualitative \ "Bhalla US. (2004) Biophys J. 87(2):733-44 ( peer-reviewed publication )" \ "Exact GENESIS implementation" "Approximates original data " -1 -12 0 simundump xgraph /graphs/conc1 0 0 1000 0 1 0 simundump xgraph /graphs/conc2 0 0 1000 0 1 0 simundump xgraph /moregraphs/conc3 0 0 100 0 1 0 simundump xgraph /moregraphs/conc4 0 0 100 0 1 0 simundump xcoredraw /edit/draw 0 -18.348 1 -27.006 -8 simundump xtree /edit/draw/tree 0 \ /kinetics/#[],/kinetics/#[]/#[],/kinetics/#[]/#[]/#[][TYPE!=proto],/kinetics/#[]/#[]/#[][TYPE!=linkinfo]/##[] \ "edit_elm.D ; drag_from_edit.w " auto 0.6 simundump xtext /file/notes 0 1 xtextload /file/notes \ "Derived from pka21.g," \ "identical except for renaming," \ "cleanups and getting rid of a " \ "couple of unused enzyme sites of" \ "PKA" addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/PKA/R2C2 REAC A B addmsg /kinetics/PKA/R2C2 /kinetics/PKA/cAMP-bind-site-B1 SUBSTRATE n addmsg /kinetics/PKA/cAMP.R2C2 /kinetics/PKA/cAMP-bind-site-B1 PRODUCT n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-B1 SUBSTRATE n addmsg /kinetics/PKA/cAMP.R2C2 /kinetics/PKA/cAMP-bind-site-B2 SUBSTRATE n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-B2 SUBSTRATE n addmsg /kinetics/PKA/cAMP2.R2C2 /kinetics/PKA/cAMP-bind-site-B2 PRODUCT n addmsg /kinetics/PKA/cAMP2.R2C2 /kinetics/PKA/cAMP-bind-site-A1 SUBSTRATE n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-A1 SUBSTRATE n addmsg /kinetics/PKA/cAMP3.R2C2 /kinetics/PKA/cAMP-bind-site-A1 PRODUCT n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-A2 SUBSTRATE n addmsg /kinetics/PKA/cAMP3.R2C2 /kinetics/PKA/cAMP-bind-site-A2 SUBSTRATE n addmsg /kinetics/PKA/cAMP4.R2C2 /kinetics/PKA/cAMP-bind-site-A2 PRODUCT n addmsg /kinetics/PKA/cAMP4.R2C2 /kinetics/PKA/Release-C1 SUBSTRATE n addmsg /kinetics/PKA-active /kinetics/PKA/Release-C1 PRODUCT n addmsg /kinetics/PKA/cAMP4.R2C /kinetics/PKA/Release-C1 PRODUCT n addmsg /kinetics/PKA/cAMP4.R2C /kinetics/PKA/Release-C2 SUBSTRATE n addmsg /kinetics/PKA-active /kinetics/PKA/Release-C2 PRODUCT n addmsg /kinetics/PKA/cAMP4.R2 /kinetics/PKA/Release-C2 PRODUCT n addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA/PKA-inhibitor REAC A B addmsg /kinetics/PKA-active /kinetics/PKA/inhib-PKA SUBSTRATE n addmsg /kinetics/PKA/PKA-inhibitor /kinetics/PKA/inhib-PKA SUBSTRATE n addmsg /kinetics/PKA/inhibited-PKA /kinetics/PKA/inhib-PKA PRODUCT n addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA/inhibited-PKA REAC B A addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/PKA/cAMP.R2C2 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/PKA/cAMP.R2C2 REAC A B addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/PKA/cAMP2.R2C2 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/PKA/cAMP2.R2C2 REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/PKA/cAMP3.R2C2 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/PKA/cAMP3.R2C2 REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/PKA/cAMP4.R2C2 REAC B A addmsg /kinetics/PKA/Release-C1 /kinetics/PKA/cAMP4.R2C2 REAC A B addmsg /kinetics/PKA/Release-C1 /kinetics/PKA/cAMP4.R2C REAC B A addmsg /kinetics/PKA/Release-C2 /kinetics/PKA/cAMP4.R2C REAC A B addmsg /kinetics/PKA/Release-C2 /kinetics/PKA/cAMP4.R2 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/Release-C1 /kinetics/PKA-active REAC B A addmsg /kinetics/PKA/Release-C2 /kinetics/PKA-active REAC B A addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA-active REAC A B enddump // End of dump call /kinetics/PKA/notes LOAD \ "General ref: Taylor et al Ann Rev Biochem 1990 59:971-1005" \ "" call /kinetics/PKA/R2C2/notes LOAD \ "This is the R2C2 complex, consisting of 2 catalytic (C)" \ "subunits, and the R-dimer. See Taylor et al Ann Rev Biochem" \ "1990 59:971-1005 for a review." \ "The Doskeland and Ogreid review is better for numbers." \ "Amount of PKA is about .5 uM." call /kinetics/PKA/cAMP-bind-site-B1/notes LOAD \ "Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M" \ "for type II, 5.6e-8 M for type I. Take mean" \ "which comes to 2e-13 #/cell" \ "Smith et al PNAS USA 78:3 1591-1595 1981 have better data." \ "First kf/kb=2.1e7/M = 3.5e-5 (#/cell)." \ "Ogreid and Doskeland Febs Lett 129:2 287-292 1981 have figs" \ "suggesting time course of complete assoc is < 1 min." call /kinetics/PKA/cAMP-bind-site-B2/notes LOAD \ "For now let us set this to the same Km (1e-7M) as" \ "site B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2)" \ "= 2e-13:2.77e-12" \ "Smith et al have better values. They say that this is" \ "cooperative, so the consts are now kf/kb =8.3e-4" call /kinetics/PKA/Release-C1/notes LOAD \ "This has to be fast, as the activation of PKA by cAMP" \ "is also fast." \ "kf was 10" \ "" call /kinetics/PKA/PKA-inhibitor/notes LOAD \ "About 25% of PKA C subunit is dissociated in resting cells without" \ "having any noticable activity." \ "Doskeland and Ogreid Int J biochem 13 pp1-19 suggest that this is" \ "because there is a corresponding amount of inhibitor protein." call /kinetics/PKA/inhib-PKA/notes LOAD \ "This has to be set to zero for matching the expts in vitro." \ "In vivo we need to consider the inhibition though." \ "" \ "" call /kinetics/PKA/cAMP.R2C2/notes LOAD \ "CoInit was .0624" \ "" call /kinetics/PKA/cAMP4.R2/notes LOAD \ "Starts at 0.15 for the test of fig 6 in Smith et al, but we aren't using" \ "that paper any more." call /kinetics/cAMP/notes LOAD \ "The conc of this has been a problem. Schaecter and Benowitz use 50 uM," \ "but Shinomura et al have < 5. So I have altered the cAMP-dependent " \ "rates in the PKA model to reflect this." call /kinetics/PKA-active/notes LOAD \ "Conc of PKA in brain is about 1 uM" call /kinetics/doqcsinfo/notes LOAD \ "General ref: Taylor et al Ann Rev Biochem 1990 59:971-1005" complete_loading