Dynamic localization of hepatocellular transporters in health and disease

Figure 4 Signaling pathways involved in the exocytic insertion of canalicular transporters promoted by cAMP and by TC and TUDC. cAMP effect involves elevation in cytosolic Ca²⁺ and activation of the PI3K-dependent pathway. Formation of the CaM complex promotes apical insertion of transporters via unidentified mediators, and is counter-regulated by activation of cPKC. PI3K promotes exocytic insertion of canalicular transporters by activation of PKCδ and Erk-1 and Erk-2 of MAPK, via the Ras/Raf- MAPK kinase (MEK)-Erk-1/2 pathway. TC and TUDC also evoke the PI3K-dependent signaling pathway and promote insertion of canalicular transporters via the Ras/Raf-MEK-Erk-1/2 pathway. TUDC also stimulates canalicular carrier insertion by activation of MAPKs of the p38MAPK type, by an unknown mechanism.