Structure and regulation of MAPK phosphatases

Amjad Farooq, Ming Ming Zhou

Research output: Contribution to journalArticle

339 Citations (Scopus)

Abstract

MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (DS-MKPs). Recent studies reveal that substrate specificity and enzymatic activity of MKPs are tightly controlled not only by the conserved C-terminal phosphatase domain but also by an N-terminal (NT) kinase-binding domain. Notably, MKPs that consist of a kinase-binding domain and a phosphatase domain exhibit little phosphatase activity in the absence of their physiological substrates. MKP binding to a specific MAPK results in enzymatic activation of the phosphatase in a substrate-induced activation mechanism. This direct coupling of inactivation of an MAPK to activation of an MKP provides a tightly controlled regulation that enables these two key enzymes to keep each other in check, thus guaranteeing the fidelity of signal transduction. This review discusses the recent understanding of structure and regulation of the large family of dual specificity MKPs, which can be divided into four subgroups according to their functional domains and mechanism of substrate recognition and enzymatic regulation. Moreover, detailed comparison of the structural basis between this unique substrate-induced activation mechanism and the common auto-inhibition mechanism is provided.

Original languageEnglish
Pages (from-to)769-779
Number of pages11
JournalCellular Signalling
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

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Phosphoric Monoester Hydrolases
Phosphotransferases
Signal Transduction
Substrate Specificity
Enzymes

Keywords

  • Dual specificity MAPK phosphatases
  • MAPK phosphatases
  • N-terminal

ASJC Scopus subject areas

  • Cell Biology

Cite this

Structure and regulation of MAPK phosphatases. / Farooq, Amjad; Zhou, Ming Ming.

In: Cellular Signalling, Vol. 16, No. 7, 01.07.2004, p. 769-779.

Research output: Contribution to journalArticle

Farooq, Amjad ; Zhou, Ming Ming. / Structure and regulation of MAPK phosphatases. In: Cellular Signalling. 2004 ; Vol. 16, No. 7. pp. 769-779.
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