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Review
. 2002 Jun 26;3(7):REVIEWS3009.
doi: 10.1186/gb-2002-3-7-reviews3009. Epub 2002 Jun 26.

MAP kinase phosphatases

Aspasia Theodosiou  1 , Alan Ashworth
Affiliations
Review

MAP kinase phosphatases

Aspasia Theodosiou et al. Genome Biol. .

Abstract

Mitogen-activated protein MAP kinases are key signal-transducing enzymes that are activated by a wide range of extracellular stimuli. They are responsible for the induction of a number of cellular responses, such as changes in gene expression, proliferation, differentiation, cell cycle arrest and apoptosis. Although regulation of MAP kinases by a phosphorylation cascade has long been recognized as significant, their inactivation through the action of specific phosphatases has been less studied. An emerging family of structurally distinct dual-specificity serine, threonine and tyrosine phosphatases that act on MAP kinases consists of ten members in mammals, and members have been found in animals, plants and yeast. Three subgroups have been identified that differ in exon structure, sequence and substrate specificity.

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Figures

Figure 1
Figure 1
Gene structure of the DUSPs. Three distinct gene structures have been described for the DUSPs, allowing their classification into subgroups I, II and III. Structural motifs (CH2 domains, docking domain and catalytic domain) in the encoded proteins are indicated by shaded shapes and exons by boxes and roman numerals. The dashed box in subgroup II is an alternatively spliced exon.
Figure 2
Figure 2
Phylogenetic analysis of DUSP sequences. Human DUSP amino-acid sequences were aligned and a phylogenetic tree derived using Clustal W [68] on DNASTAR. The length of the branches is proportional to sequence divergence between proteins. Subgroups I, II, and III are shaded (see text for further details).
Figure 3
Figure 3
Three-dimensional structure of DUSP6. (a) The amino-terminal Erk-binding (EB) domain, reproduced with permission from [38]. (b) The catalytic domain, reproduced with permission from [24].
Figure 4
Figure 4
Classification of DUSPs on the basis of MAP kinase docking site. The sequence thought to be responsible for MAP kinase interaction in DUSPs is shown, as is substrate preference. This results in a DUSP subclassification similar to that obtained by analysis of gene structure (Figure 1) or amino-acid sequence similarity (Figure 2). Adapted from [14].
Figure 5
Figure 5
Activation of DUSP6 phosphatase by interaction with substrate ERK. This is a simplified schematic representation of ERK binding to DUSP6, resulting in catalytic activation. The carboxy-terminal catalytic domain is represented by a circle and the amino terminus containing the ERK binding (EB) domain by a rectangle. DUSP6 appears to exist in a low-activity state until binding to ERK through the EB domain results in a conformational change, triggering activation of the phosphatase. This results in ERK dephosphorylation and subsequent dissociation of the complex.
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References

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