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

Citation
Cr. Lu et al., Intracrine hepatopoietin potentiates AP-1 activity through JAB1 independent of MAPK pathway, FASEB J, 15(13), 2001, pp. NIL_221-NIL_238
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Experimental Biology
Journal title
FASEB JOURNAL
ISSN journal
0892-6638 → ACNP
Volume
15
Issue
13
Year of publication
2001
Pages
NIL_221 - NIL_238
Database
ISI
SICI code
0892-6638(200111)15:13<NIL_221:IHPAAT>2.0.ZU;2-N
Abstract
Many growth factors and cytokines are involved in liver regeneration. Of th em, only hepatopoietin (HPO)/ALR (augmenter of liver regeneration) is a spe cifically hepatotrophic factor originally identified from the cytosol of re generating or hyperplastic hepatic cells. Previous reports indicate that ex tracellular HPO triggers the MAPK pathway by binding its specific receptor on the cell surface. However, its function in the cytosol of hepatocytes is unclear. Here we identified that JAB1 (Jun activation domain-binding prote in 1), a co-activator of AP-1, which is essential for liver regeneration, s pecifically interacts with intracellular HPO. JAB1 colocalizes with HPO in nuclei of hepatic cells or COS-7 cells. As an intracrine factor, the intrac ellular function of HPO is to increase c-Jun phosphorylation independent of c-Jun amino-terminal kinase (JNK), extracellular signal-regulated kinase ( ERK) -1 and -2, and leads to potentiation of JAB1-mediated AP-1 activation. Amino acids 1-63 of HPO molecule are sufficient to bind to JAB1, but the f ull-length HPO is necessary for its intracellular signaling. Taken together , these results elucidate a novel mechanism of intracrine cytokine signalin g by specifically modulating the AP-1 pathway through JAB1, in a MAPK-indep endent fashion.