Abstract
Extracellular signal-regulated kinase-1 and -2 (ERK1/2) are activated by dual threonine and tyrosine phosphorylation of a TEY motif The highly related kinase ERK5 is also activated by phosphorylation at a TEY motif. Inactivation of ERK1/2 is achieved by distinct members of the dual-specificity protein phosphatase (DUSP) family, which are responsible for the specific, regulated de-phosphorylation of the TEY motif. These include both nuclear (DUSP5) and cytoplasmic (DUSP6) enzymes. DUSP6, a candidate tumour suppressor gene, is thought to be highly specific for inactivation of ERK1/2 but several reports have suggested that it may also inactivate ERK5. Here we have compared the ability of DUSP6 to regulate the ERK1/2 and ERK5 protein kinases. We find that DUSP6 binds to ERK1/2 in both yeast and human cells but fails to bind to ERK5. Recombinant ERK2 can induce catalytic activation of DUSP6 whereas ERK5 cannot. Ectopic expression of DUSP6 can de-phosphorylate a co-expressed ERK2 construct but does not de-phosphorylate ERK5. Finally, expression of DUSP6 blocks the MEK1-driven activation of GAL4-ELK1, an ERK1/2-regulated transcription factor, but fails to block the MEK5-driven activation of GAL4-MEF2D, an ERK5-regulated transcription factor. These results demonstrate that even upon over-expression DUSP6 fails to inactivate ERK5, confirming that it is indeed an ERK1/2-specific DUSP. (C) 2008 Elsevier Inc. All rights reserved.
Original language | English |
---|---|
Pages (from-to) | 836-843 |
Number of pages | 8 |
Journal | Cellular Signalling |
Volume | 20 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2008 |
Keywords
- DUSP6
- ERK1/2
- ERK5
- MKP-3
- ACTIVATED PROTEIN-KINASE
- DUAL-SPECIFICITY PHOSPHATASE
- MAP KINASE
- SIGNAL-TRANSDUCTION
- CATALYTIC ACTIVATION
- PHYSIOLOGICAL FUNCTIONS
- GROWTH-FACTOR
- CELL-CYCLE
- RECEPTOR
- PATHWAY