Fig. 2: Proteasomal degradation of DUSP6 sustains HER2 phospho-activation. | Nature Communications

Fig. 2: Proteasomal degradation of DUSP6 sustains HER2 phospho-activation.

From: Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer

Fig. 2

a Western blots showing changes in the indicated DUSPs following treatment with trametinib or ulixertinib overnight (~16 h) in the two different PDAC lines. b Immunoprecipitation (IP) experiment showing polyubiquitination of stably expressed FLAG-tagged DUSP4 and DUSP6 in 293 T cells following 16 h treatment with ulixertinib followed by co-treatment with DMSO or bortezomib for 6 h. c Western blots showing changes in p-HER2 (Y1248), p-ERK1/2, DUSP4, and DUSP6 levels in Pa01c and HPAC cells treated with trametinib or ulixertinib for 16 h, followed by DMSO or bortezomib for 6 h. d Western blots showing changes in p-HER2 and p-ERK1/2 in Pa01c and HPAC cells stably expressing scramble control of two different shRNAs against DUSP4 or DUSP6. e Western blots showing changes in p-HER2 and p-ERK1/2 in Pa01c and HPAC cells stably overexpressing an empty vector, DUSP6, DUSP4, or DUSP7. f Western blots showing changes in p-HER2 and p-ERK1/2 levels in Pa01c and HPAC cells stably expressing wild-type (WT) or enzymatically inactive (C293S) DUSP6. All experiments were conducted two times, and one set of data for each was presented. Source data are provided in Source Data file.

Back to article page