Intracrine hepatopoietin potentiates AP-1 activity through JAB1 independent of MAPK pathway

SPECIFIC AIMSHepatopoietin (HPO) is a specifically hepatotropic factor originally identified from the cytosol of regenerating or hyperplastic hepatic cells. Although previous results showed that extracellular HPO triggers the MAPK signal transduction by binding to its specific receptor on the cell surface, leading to the proliferation of hepatocyte, the intracellular action of HPO is unclear. The aim of the study is to investigate the possible intracellular function or signaling pathway of HPO.PRINCIPAL FINDINGS1. HPO interacts with JAB1 in the yeast two-hybrid systemUsing the yeast two-hybrid system to screen the HPO-interacting protein(s), we identified several types of clones that interacted specifically with HPO. One contained a cDNA insert with almost the entire coding sequence (amino acids 39–335) of human JAB1 (Jun-activating domain binding protein 1), a coactivator of AP-1. Either JAB1 deletant (amino acids 39–335) or wild-type JAB1 (amino acids 1–335) interacts with HPO similarly. Additional resu...