Figure Legends, Supplemental Computational/Experimental Procedures/Analysis

作者: Alejandra C Ventura , Alan Bush , Gustavo Vasen , Matías A Goldín , Brianne Burkinshaw

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摘要: In the three models, left panels contain schemas of the corresponding model, middle panels show dose‐responses and right panels show temporal dynamics. Parameters were selected so that X* has a transient behavior. Dose‐responses are included for the equilibrium value of C (ligand‐receptor complex) in solid black lines, and for the maximum of X* in dashed blue lines. The dose of the ligand is normalized by the Kd of the binding/unbinding reaction. Temporal profiles of C (solid lines) and of X*(dashed lines) are included at ligand concentrations indicated over the traces.A. X with an inactive refractory state (same as in Figure 2). Left. Occupied receptor activates effector X; after a while, active X (X*) converts into an inactive refractory state (X^), which slowly converts back to the inactive form (X), closing the cycle. Middle. Parameter values: k‐= 0.001 1/sec, r1= 0.1, r2= 0.06‐0.8‐1.6 (increasing from left to right in the middle panel), r3= 0.001, Xtot= 10 (k+ is not needed because of the dimensionless variables chosen, see section 1). EC50 for each response: 1 for C, and for X* is 9.3 for r2= 0.06, 65.8 for r2= 0.8, and 87 for r2= 1.6. Right. Temporal profiles for the same parameters as in the middle panel, using r2= 0.8. B. X controlled by an incoherent feed‐forward loop (IFFL). Left. Occupied receptor activates both B and X into B* and X*, and B* increases X* inactivation. Middle. Parameter values: k‐= 0.001‐0.1 1/sec (from right to left), kCB= 0.5, KCB= 0.01, kFBB= 10, KFBB= 10, FB= 0.5, kCX= 2, KCX= 0.1, kBX= 3, KBX= 0.1 (see SI Appendix, Section 2 for details of the model, ki are catalytic rate constants and Ki are Michaelis‐Menten constants, for …

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