TI  - <prot>Inhibin</prot> antagonizes inhibition of liver cell growth by activin by a
      dominant-negative mechanism.
PG  - 6308-13
AB  - The beta:   <prot>beta activin</prot>   homodimer and  alpha : <prot>beta inhibin</prot>  heterodimer are
      mutual antagonists which share a common beta subunit. Recently, it has
      been shown that, similar to <prot>transforming growth factor-beta 1</prot>, activin is
      an inhibitor of hepatocyte DNA synthesis. The activin receptor appears to
      be an obligatory complex of genetically distinct type I and II
      transmembrane serine/threonine kinases. Activin type I receptors, <prot>SKR1</prot> and
      <prot>SKR2</prot>, were first cloned from well differentiated human hepatoma cells
      (HepG2). This prompted us to investigate the binding of activin and
      inhibin to receptors from HepG2 cells and the effect of the two ligands on
      DNA synthesis. Here we show that  beta:<prot>beta activin</prot>  binds to the  <prot>activin
      type II receptor kinase</prot> (<prot>ActRII</prot>)  which induces  activin  binding to the  type
      I receptor kinase <prot>SKR2</prot>  to form <prot>ActRII</prot>.beta:beta.<prot>SKR2</prot> complexes in which an
      <prot>activin beta</prot> chain occupies each receptor subunit.  <prot>Inhibin</prot>  also binds to
       <prot>ActRII</prot>  through its beta subunit, competes with the binding of  activin  to
       <prot>ActRII</prot> , but fails to form the <prot>ActRII</prot>.<prot>SKR2</prot> complex. No specific binding
      site for inhibin could be demonstrated in HepG2 cells. <prot>Inhibin</prot>, which had
      no activity of its own, antagonized the inhibitory effect of activin on
      DNA synthesis. The results suggest that inhibin may be a natural
      antagonist of assembly of the heterodimeric <prot>activin receptor</prot> complex
      through a dominant-negative mechanism.
AD  - Albert B. Alkek Institute of Biosciences and Technology, Department of
