ERK7, a member of the mitogen-activated protein kinase family, has a 
carboxyl-terminal tail that is required for ERK7 activation, cellular 
localization, and its ability to inhibit DNA synthesis. To identify proteins 
that interact with ERK7, we utilized a yeast two-hybrid screen with the 
COOH-terminal tail of ERK7 as bait and isolated the cDNA for a novel protein 
termed CLIC3. The interaction between CLIC3 and ERK7 in mammalian cells was 
confirmed by co-immunoprecipitation. CLIC3 has significant homology to human 
intracellular chloride channels 1 (NCC27/CLIC1) and 2 and bovine kidney chloride 
channel p64. Like NCC27/CLIC1, CLIC3 is predominantly localized in the nucleus 
and stimulates chloride conductance when expressed in cells. Taken together, 
these results suggest that CLIC3 is a new member of the human CLIC family. The 
observed interaction between CLIC3 and ERK7 is the first demonstration of a 
stable complex between a protein that activates chloride ion transport and a 
member of the mitogen-activated protein kinase family of signal transducers. The 
specific association of CLIC3 with the COOH-terminal tail of ERK7 suggests that 
CLIC3 may play a role in the regulation of cell growth.