AI Article Synopsis
- The orphan MAP kinase ERK5's activity is enhanced by Ras, indicating it may facilitate Raf-independent signaling.
- Raf-1 influences Ras's activation of ERK5, but this effect doesn't link to Raf-1's catalytic activity, hinting at a different regulatory mechanism.
- The ERK5/MEK5 pathway is essential for Raf-dependent cell changes, with an active MEK5 form working alongside Raf to promote transformation in certain cell types.
Article Abstract
The activity of the catalytic domain of the orphan MAP kinase ERK5 is increased by Ras but not Raf-1 in cells, which suggests that ERK5 might mediate Raf-independent signaling by Ras. We found that Raf-1 does contribute to Ras activation of ERK5 but in a manner that does not correlate with Raf-1 catalytic activity. A clue to the mechanism of action of Raf-1 on ERK5 comes from the observation that endogenous Raf-1 binds to endogenous ERK5, suggesting the involvement of regulatory protein-protein interactions. This interaction is specific because Raf-1 binds only to ERK5 and not ERK2 or SAPK. Finally, we demonstrate the ERK5/MEK5 pathway is required for Raf-dependent cellular transformation and that a constitutively active form of MEK5, MEK5DD, synergizes with Raf to transform NIH 3T3 cells. These observations suggest that ERK5 plays a large role in Raf-1-mediated signal transduction.
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| http://dx.doi.org/10.1074/jbc.274.44.31588 | DOI Listing |
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Article Synopsis
- The orphan MAP kinase ERK5's activity is enhanced by Ras, indicating it may facilitate Raf-independent signaling.
- Raf-1 influences Ras's activation of ERK5, but this effect doesn't link to Raf-1's catalytic activity, hinting at a different regulatory mechanism.
- The ERK5/MEK5 pathway is essential for Raf-dependent cell changes, with an active MEK5 form working alongside Raf to promote transformation in certain cell types.
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