Liebig’s law of the minimum in the TGF-β/SMAD pathway
Fig 2
A minimal mathematical model predicts that TGF-β signaling activity is dictated by the type of TGF-β receptor in lower abundance.
(A) A minimal model of the TGF-β pathway with two reactions including the TGF-β ligand (L), which interact with type I receptor (R1) and type II receptor (R2) with a binding affinity (K1). The active ligand-receptor complex (LRC) phosphorylates the SMAD protein with an equilibrium coefficient (K2). TGF-β signaling activity (Sa) at the steady state can be analytically calculated with equations (refer to S1 File for model details and equation derivation). (B) The response profile of TGF-β signaling activity (Sa) at the steady state is shown in relation to a 2-dimensional matrix of TGFBR1 and TGFBR2 expression numbers spanning five orders of magnitude. K1 = 1000, K2 = 10. TGF-β ligand concentration is set to be 0.1 nM.