Several members of the Ets gene family encode sequence-specific DNA binding proteins that recognize DNA sequences with a centrally located 5'-GGAA-3' element. All of the Ets proteins recognize the same central core sequence but each protein interacts with unique sequences that flank this core. PEA3 binds the motif 5'-AGGAAG-3', while ER81 (also designated ETV1) binds the motif 5'-CGGAA/T-3'. PEA3 is expressed at readily detectable levels in cells of epithelial and fibroblastic origin. Unlike other members of the Ets family, including Ets-1 and Ets-2, PEA3 is not expressed in hematopoietic cells. ER81 is highly expressed in brain, testis, lung and heart. ER81 is also moderately expressed in spleen, pancreas, colon and small intestine. During development, ER81, PEA3 and ERM display unique expression patterns which suggest these transcriptional factors play an important role in organogenesis. ERK-1 activates ER81 transcriptional activity, while MAPKAP kinase 2 inhibits ER81.