Figure 4.

ARHGAP9-mediated regulation of the MAPK signaling pathway in BC. ARHGAP9 associates specifically with ERK2 and p38α via complementarily charged residues within the WW domain of ARHGAP9 and the CD domains of ERK2 and p38α. The binding of EGF to EGFR activates EGFR, which is already overexpressed in BC. Furthermore, the Ras-MAPK pathway is activated through the MAPK/ERK pathway. The increased expression of various upstream kinases (including MEK2 and MKK3, 4 and 6, which interact with ERK2 and p38α, respectively) reduces interaction between ARHGAP9 and ERK2 and p38α in BC. ARHGAP9, Rho GTPase-activating protein 9; BC, bladder cancer.