Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses

Kate L. Jeffrey, Montserrat Camps, Christian Rommel, Charles R. Mackay

Research output: Contribution to journalReview ArticleResearchpeer-review

303 Citations (Scopus)

Abstract

Dual-specificity phosphatases (DUSPs) are a subset of protein tyrosine phosphatases, many of which dephosphorylate threonine and tyrosine residues on mitogen-activated protein kinases (MAPKs), and hence are also referred to as MAPK phosphatases (MKPs). The regulated expression and activity of DUSP family members in different cells and tissues controls MAPK intensity and duration to determine the type of physiological response. For immune cells, DUSPs regulate responses in both positive and negative ways, and DUSP-deficient mice have been used to identify individual DUSPs as key regulators of immune responses. From a drug discovery perspective, DUSP family members are promising drug targets for manipulating MAPK-dependent immune responses in a cell-type and disease-context-dependent manner, to either boost or subdue immune responses in cancers, infectious diseases or inflammatory disorders.

Original languageEnglish
Pages (from-to)391-403
Number of pages13
JournalNature Reviews Drug Discovery
Volume6
Issue number5
DOIs
Publication statusPublished - 1 May 2007
Externally publishedYes

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