Fig. 5.
Feedback mechanisms aimed at restoring MAPK signaling activity. A, Log2-fold-changes of mRNA expression plotted against mRNA half-life of regulators of major signaling pathways at 2 h. Only short-lived negative regulators of MAPK signaling respond to growth factor stimulation or BRAF inhibition. In all conditions, DUSP1, DUSP8 and DUSP10 are up-regulated in response to serum stimulation at T = 0 h. DUSP4, DUSP6 and SPRY1 are downregulated only in BRAFi treated samples, in response to BRAF inhibition. B, Scaled mRNA expression levels of a cluster of RTKs. Of the 35 RTKs, 18 are up-regulated (INSRR, ROS1, STYK1, ERBB3, FGFR2, PTK7, EPHA4, TEK, EPHB2, ERBB2, LMTK3, MERTK, INSR, EPHA10, NTRK1, DDR1). C, mRNA expression of ERBB2. D, mRNA expression of ERBB3. E, mRNA expressions of ERBB2 and ERBB3 in SNU-C5, VACO432, and KM-20 BRAF(V600E) CRC cell lines. F, Phosphorylation expression of the negative regulator ERRFI1 is downregulated at residue S251 in BRAFi samples.