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This study demonstrates that PP1\/PP2A are activated vasoactive intestinal peptide (VIP)\/secretin in pancreatic acini. VIP\/secretin both activate PP1\/PP2A but differed for their ability to activate exchange protein directly activated by cAMP (EPAC) and protein kinase A (PKA). VIP\/secretin require PAK4, not PAK2, activation to stimulate PP2A, not PP1; however, PP1\/PP2A activation stimulate sodium-potassium adenosine triphosphatase (Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase) activity. 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