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【正文】 city the autophosphorylation steps are represented by a single enzyme arrow in this figure, with CaMKII_a as the bined activity of the various phosphorylation states. The individual kiic terms used in the model are indicated by the multiple rate references on the arrows. Reaction I: CaMKII Reaction J: PKA Reaction K: PKC Reaction L: Ca, IP3 Reaction M: CaM Reaction N: CaN Reaction O: PP1 三 、 establishing the individual pathways 1. steps 1. Set up model activation of single ponent. the model for an individual signaling pathway. 3. Obtain a good empirical model which fit the experimental data. experimentally defined bination of 2 or 3 such individual signaling pathways. these bined models. 2. Materials and methord (1). Hippocampal CA1 neuron(in GENSIS), (2).NMDAR[on dendritic spine(樹突棘 ) on the model] (3).Synaptic input(3 tetanic bursts at 100HZ,1s each) →LTP →Ca2+ waveforms 3. Computation formulation Genesis formulation: S + E k2k1 SE k3 P + E Vmax = max velocity = k3. Substrate is saturating, so all of E is in SE form. So Vmax.[Etot] = [SE].k3 == [Etot].k3 Km = (k3 + k2)/k1 k2 = k3 * 4 Kd=Kb/Kf If [A]*[Bhalf]*Kf=[Chalf=Bhalf]*Kb then [A]=Kb/Kf=Kd Ka=Kf/Kb=1/Kd ? (i). Model simple kiic schemes ? that could be calculated analytically, ? pare simulated results with analytical results. ? (ii). Use the law of mass conservation and ? microscopic reversibility principles(微觀可逆性原理 ) ? →test accuracy in plex reaction schemes. ? (iii). Run the same model at different time steps, ? pare the resulting simulated values. 5. Protein Kinase C modeling example Simulation parameters: PKC Reaction K: PKC References Figure Reac kf kb K 1 1 50 K 2 2E10 K 3 K 4 K 5 1 K 6 2 K 7 K 8 K 9 K 10 2 References Concs K: PKC References Figure Name Conc K PKC_inactive 1 1. Review: Y. Nishizuka, Nature 334, 661 (1988) 2. J. D. Schaechter and L. I. Benowitz, J. , 4361 (1993) 3. T. Shinomura, Y. Asaoka, M. Oka, K. Yoshida, Y. Nishizuka, Proc. Natl. Acad. Sci. . 88, 5149 (1991) U. Kikkawa, Y. Takai, R. Minakuchi, S. Inohara, Y. Nishizuka, J. Biol. Chem. 257, 13341 (1982). A. Block diagram of activation for PKC pathway by Ca2+, AA and DAG. ? built up simulations iteratively: ? First: matched AA activation of PKC at zero Ca. ? Then: matched activation of PKC with Ca at zero AA, ? Third: matched the curves in B with 1 uM Ca and varying AA. ? Four: test the match for C, with varying Ca and 50 uM AA. ? Last:incorporated DAG interactions into the model. B: Activation of PKC by AA, with (triangles) or without (squares) 1 mM Ca2+. ? Open symbols and dashed lines represent simulations, solid symbols and solid lines are experimental data. Shows:Ca2+ is necessary for the activation of PKC. ?experimental concentrationeffect curves from two main sources: ?J. D. Schaechter and L. I. Benowitz, J. Neurosci. 13, 4361 (1993)。 激活多種酶和依賴 cGMP的蛋白激酶而發(fā)揮生理作用。 Ca2+ /CaM PKC* 使各種受體，膜蛋白，收縮蛋白，細(xì)胞骨架蛋白，核蛋白和酶類的 絲氨酸或蘇氨酸殘基磷酸化 ，從而影響細(xì)胞代謝、生長(zhǎng)和分化。 ? Some of the developmental distortions in roots induced on addition of RALF are reminiscent of impaired nonpeptide hormonecontrolled processes. 因此，揭開兩種信號(hào) cascades之間關(guān)系，將是非常有趣的事。 ? 快速引起 medium 堿化 From the followings support the idea that peptide and nonpeptide hormoneactivate
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