The COP9 signalosome (CSN) is a complex of eight proteins first identified as a 
repressor of plant photomorphogenesis. A protein kinase activity associated with 
the COP9 signalosome has been reported but not identified; we present evidence 
for inositol 1,3,4-trisphosphate 5/6-kinase (5/6-kinase) as a protein kinase 
associated with the COP9 signalosome. We have shown that 5/6-kinase exists in a 
complex with the eight-component COP9 signalosome both when purified from bovine 
brain and when transfected into HEK 293 cells. 5/6-kinase phosphorylates the 
same substrates as those of the COP9 signalosome, including IkappaBalpha, p53, 
and c-Jun but fails to phosphorylate several other substrates, including c-Jun 
1-79, which are not substrates for the COP9-associated kinase. Both the COP9 
signalosome- associated kinase and 5/6-kinase are inhibited by curcumin. The 
association of 5/6-kinase with the COP9 signalosome is through an interaction 
with CSN1, which immunoprecipitates with 5/6-kinase. In addition, the inositol 
kinase activity of 5/6-kinase is inhibited when in a complex with CSN1. We 
propose that 5/6-kinase is the previously described COP9 signalosome-associated 
kinase.