Phospholipase C and two inositol polyphosphate (IP) kinases constitute a si
gnaling pathway that regulates nuclear messenger RNA export through product
ion of inositol hexakisphosphate (IP6). The inositol 1,4,5-trisphosphate ki
nase of this pathway in Saccharomyces cerevisiae, designated Ipk2, was foun
d to be identical to Arg82, a regulator of the transcriptional complex ArgR
-Mcm1. Synthesis of inositol 1,4,5,6-tetrakisphosphate, but not IP6, was re
quired for gene regulation through ArgR-Mcm1. Thus, the phospholipase C pat
hway produces multiple IP messengers that modulate distinct nuclear process
es. The results reveal a direct mechanism by which activation of IP signali
ng may control gene expression.