Fig. 1.

(A–D). PAK1 is overexpressed and activated in IBD. (A) Human colonic tissue stained for PAK1. PAK1 expression increases in comparison to normal mucosa at the luminal epithelial surface and crypts in both Crohn's disease (CD), ulcerative colitis (UC), and in tumors of colitis associated cancer (CAC). (B) Box plots compare mean PAK1 immunoreactivity scores (IRS) in normal mucosa (n = 6), CD (n = 7), and UC (n = 6) at the luminal surface and crypts. PAK1 is overexpressed in CAC (n = 8). The circle is the outlier from the boxplot. (C) Human colonic tissue stained for p-PAK1. In CD and UC, PAK1 activation in epithelial cells is found at the membrane, specifically at the luminal surface, but not in the crypts. In CAC, PAK1 phosphorylation is found within the nuclei and cytoplasm of tumor cells. (D) Inflammatory cytokines activate PAK1 in HCEC-1CT. WB of HCEC-1CT RIPA whole cell lysates using 50 μg protein. Cells were either untreated (Con) or treated with IFNγ, IL-1β, or TNFα for 5–60 min and analyzed for PAK1 activation with a p-PAK1 Thr 423 antibody. TNFα induced the most profound effect in PAK1 activation at 30 min. α-Tubulin was utilized as a loading control.