ERK7 is an autoactivated member of the MAPK family

Extracellular signal-regulated kinase 7 (ERK7) shares significant sequence homology with other members of the ERK family of signal transduction protei ns, including the signature TEY activation motif. However, ERK7 has several distinguishing characteristics. Unlike other ERKs, ERK7 has been shown to have significant constitutive activity in serum-starved cells, which is not increased further by extracellular stimuli that typically activate other m embers of the mitogen-activated protein kinase (MAPK) family. On the other hand, ERK7's activation state and kinase activity appear to be regulated by its ability to utilize ATP and the presence of its extended C-terminal reg ion. In this study, we investigated the mechanism of ERK7 activation, The r esults suggest that 1) MAPK kinase (MEK) inhibitors do not suppress ERK7 ki nase activity; 2) intramolecular autophosphorylation is sufficient for acti vation of ERK7 in the absence of an upstream MEK; and 3) multiple regions o f the C-terminal domain of ERK7 regulate its kinase activity. Taken togethe r, these results indicate that autophosphorylation is sufficient for ERK7 a ctivation and that the C-terminal domain regulates its kinase activity thro ugh multiple interactions.