Figure 4.

Differentially phosphorylated nucleophosmin (NPM) sites localize near its structural and functional domains. Location of NPM phosphosites detected in postischemic proximal tubule epithelial cells (PTECs), kidney tissue, and urine. Therapeutic peptide 2 (representing NPM amino acids 78–103) and 3 (representing NPM amino acids 226–246) were designed to interfere with NPM functions at the indicated phospho-sites differentially phosphorylated during ischemic stress. Site-specific amino acid substitutions were made to render each site either constitutively phosphorylated (E substituted for S or T) or constitutively dephosphorylated (A substituted for S or T) to replicate the phosphorylation status of wild-type NPM under resting or ischemic stress conditions (as described in Figure 2D).