The role of ERK-1 and ERK-2 in wild-type (wt) Ha-Ras, phorbol 12- myristate 13-acetate (PMA), and serum-induced AP-1 activity was studied. Microinjection of ERK-specific substrate peptides inhibited the induction of AP-1 activity by all three stimuli, whereas a control peptide had no effect. By using eukaryotic expression constructs encoding wt ERK-1 and kinase- deficient mutants of ERKs 1 and 2, it was found that ERK-1 and ERK-2 activities are required for AP-1 activation stimulated by either wt Ha-Ras, PMA, or serum. Overexpression of ERK-1 augmented wt Ha-Ras stimulation of AP- 1, while having no effect upon PMA or serum stimulation. Overexpression of either kinase-deficient ERK-1 or kinase-deficient ERK-2 partially inhibited AP-1 activation by wt Ha-Ras but had no effect on PMA or serum-induced activation. Coexpression of both interfering mutants abolished AP-1 induction by wt Ha-Ras, PMA, or serum. We conclude that ERKs are necessary components in the pathway leading to the activation of AP-1 stimulated by these agents.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Apr 26 1994|
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