Extracellular signal-regulated kinase 7 (ERK7), a novel ERK with a C-terminal domain that regulates its activity, its cellular localization, and cellgrowth

Mitogen-activated protein (MAP) kinases play distinct roles in a variety of cellular signaling pathways and are regulated through multiple mechanisms. In this study, a novel 61-kDa member of the MAP kinase family, termed extr acellular signal-regulated kinase 7 (ERK7), has been cloned and characteriz ed. Although it has the signature TEY activation motif of ERK1 and ERK2, ER K7 is not activated by extracellular stimuli that typically activate ERK1 a nd ERK2 or by common activators of c-Jun N-terminal kinase (JNK) and p38 ki nase. Instead, ERK7 has appreciable constitutive activity in serum starved cells that is dependent on the presence of its C-terminal domain, Interesti ngly, the C-terminal tail, not the kinase domain, of ERK7 regulates its nuc lear localization and inhibition of growth, Taken together, these results e lucidate a novel type of MAP kinase whereby interactions via its C-terminal tail, rather than extracellular signal-mediated activation cascades, regul ate its activity, localization, and function.