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. 2022 Jun 13;18(6):e10670. doi: 10.15252/msb.202110670

Figure EV1. ERK dynamics evoked by optoFGFR versus endogenous RTKs highlight different MAPK regulatory mechanisms.

Figure EV1

  • A, B
    MaxPeak and ERKpostStim quantifications of ERK responses for each stimulation pattern shown in Fig 2C (N min = 63 cells per condition). MaxPeak was quantified within a 10 min time window following the first stimulation pulse. ERKpostStim was extracted 9 min after the last pulse. Statistical analysis was done using a Wilcoxon test comparing each condition to the 20‐min interval pattern (NS: non‐significant, FDR P‐value correction method).
  • C, D
    MaxPeak and FWHM quantification of ERK responses shown in Fig 3A (N min = 150 cells per condition) (C) and in Fig 3B (N min = 130 cells per condition) (D).
  • E
    Mathematical model topology consisting of the RAS GTPase, the MAPK three‐tiered (RAF, MEK, ERK) network and the ERK‐KTR reporter. EGFR and optoFGFR inputs both activate the RAS/RAF/MEK/ERK cascade, but the ERK‐RAF NFB is not present. The EGFR activity is under receptor‐dependent regulations.
  • F
    Simulation of ERK responses from the training dataset (Fig 3E), including the maximum a posteriori (MAP) estimate, the posterior envelope indicating the predictive density of our estimation, as well as an example trajectory.
  • G
    Predictions of the model for ERK responses evoked by 1 ng/ml EGF, 100 ng/ml EGF, and sustained high optoFGFR inputs.
  • H
    Mathematical model topology consisting of the RAS GTPase, the MAPK three‐tiered (RAF, MEK, ERK) network and the ERK‐KTR reporter. EGFR and optoFGFR inputs both activate the RAS/RAF/MEK/ERK cascade and the ERK‐RAF NFB. The receptor‐dependent regulation of EGFR was removed.
  • I
    Simulation of ERK responses from the training dataset (Fig 3E), including the maximum a posteriori (MAP) estimate, the posterior envelope indicating the predictive density of our estimation, as well as an example trajectory.
  • J
    Predictions of the model for ERK responses evoked by 1 ng/ml EGF, 100 ng/ml EGF, and sustained high optoFGFR inputs.
  • K
    ERK responses to sustained optoFGFR input (D = 18 mJ/cm2) under dose response inhibition with the FGFR inhibitor (SU5402).

Data information: (A–D) boxes indicate the upper and lower quartiles, the central bands indicate the median, and whiskers extend to individuals up to 1.5 interquartile away from the median.