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The carboxyl-terminal domains of MKP-1 and MKP-2 have inhibitory effects on their phosphatase activity

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Abstract

Both the mitogen-activated protein kinase (MAPK) phosphatases MKP-1 and MKP-2 exert important feedback control of MAPK-mediated signaling events. The function of MKP-1 and MKP-2 is regulated via complex mechanisms, ranging from increased transcription of the MKP-1 and MKP-2 genes to post-translational catalytic activation of MKP-1 and MKP-2 proteins upon binding to their substrate MAPKs. In addition, MKP-1 stability increases upon ERK-dependent phosphorylation of two serine residues in its C-terminus. The C-terminal regions of MKP-1 and MKP-2, but not those of other MKPs, are homologous. To investigate the role of this domain, we have deleted the C-terminal tails from MKP-1 and MKP-2 and examined the effect of these deletions on their enzymatic activity. C-terminally truncated MKP-1 and MKP-2 exhibited, both in vivo and in vitro, substantially greater phosphatase activity towards their substrate MAPKs than did the full-length counterparts. However, C-terminal truncations did not significantly change either their substrate affinity, or their substrate-mediated catalytic activation. Basal phosphatase activity of the truncated proteins was also significantly higher than that of the wild-type counterparts. Collectively, these results suggest that the C-terminal domain may potentially play a role in the regulation of MKP-1 and MKP-2.

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Authors
  1. Dorothy Hutter
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  2. Peili Chen
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  3. Janice Barnes
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  4. Yusen Liu
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Hutter, D., Chen, P., Barnes, J. et al. The carboxyl-terminal domains of MKP-1 and MKP-2 have inhibitory effects on their phosphatase activity. Mol Cell Biochem 233, 107–117 (2002). https://doi.org/10.1023/A:1015502226940

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