Liebig’s law of the minimum in the TGF-β/SMAD pathway
Fig 3
Computational modeling of heterogeneous signaling responses in the variation space of TGF-β receptors and SMAD2 expression.
(A) Scheme of the extended TGF-β signaling model. The development of the extended model is described in the S1 File. (B) Heterogeneous expression of TGF-β receptors and SMAD2 is illustrated as points in 3 multi-dimensional spaces. The two magnified circles exemplify two possible expression profiles of TGFBR1, TGFBR2 and SMAD2. (C) Model predictions for normalized P-SMAD2 responses in the expression space of TGFBR1, TGFBR2 and SMAD2. Each scatter point indicates a random set of protein expression levels in the space. The point colors indicate the normalized P-SMAD2 responses (P-SMAD2/SMAD2). (D) Contour landscape of the normalized P-SMAD2 responses to the combinations of TGFBR1 and TGFBR2. The dashed line indicates relationship between the relative P-SMAD2 level and the receptors when equal amounts of each receptor are present. The abundances of TGFBR1 and TGFBR2 in HaCaT, RH-30 and HepG2 cell lines are mapped according to the relative expression data shown in Fig 3E and the measured HaCaT TGF-β receptor number shown in Fig B in S1 File. The dashed arrows indicate the directions of receptor changes. (E) TGF-β receptor expression profiles for HaCaT, RH-30 and HepG2 cell lines. Bars indicate expression levels of each receptor (normalized transcripts per million, nTPM). The data is based on the Human Protein Atlas database version 22.0.