Pseudokinases-remnants of evolution or key allosteric regulators?

Elton Zeqiraj, Daan M. F. van Aalten

    Research output: Contribution to journalArticle

    92 Citations (Scopus)

    Abstract

    Protein kinases provide a platform for the integration of signal transduction networks. A key feature of transmitting these cellular signals is the ability of protein kinases to activate one another by phosphorylation. A number of kinases are predicted by sequence homology to be incapable of phosphoryl group transfer due to degradation of their catalytic motifs. These are termed pseudokinases and because of the assumed lack of phosphoryltransfer activity their biological role in cellular transduction has been mysterious. Recent structure-function studies have uncovered the molecular determinants for protein kinase inactivity and have shed light to the biological functions and evolution of this enigmatic subset of the human kinome. Pseudokinases act as signal transducers by bringing together components of signalling networks, as well as allosteric activators of active protein kinases.

    Original languageEnglish
    Pages (from-to)772-781
    Number of pages10
    JournalCurrent Opinion in Structural Biology
    Volume20
    Issue number6
    Early online date10 Nov 2010
    DOIs
    Publication statusPublished - Dec 2010

    Keywords

    • Dependent protein kinase
    • Acute lymphoblastic leukemia
    • Guanylate Cyclase C
    • Crystal structure
    • Tyrosine kinase
    • JAK2 mutation
    • Structural analysis
    • Toxoplasma gondii
    • Polycythemia vera
    • Catalytic subunit

    Cite this

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    title = "Pseudokinases-remnants of evolution or key allosteric regulators?",
    abstract = "Protein kinases provide a platform for the integration of signal transduction networks. A key feature of transmitting these cellular signals is the ability of protein kinases to activate one another by phosphorylation. A number of kinases are predicted by sequence homology to be incapable of phosphoryl group transfer due to degradation of their catalytic motifs. These are termed pseudokinases and because of the assumed lack of phosphoryltransfer activity their biological role in cellular transduction has been mysterious. Recent structure-function studies have uncovered the molecular determinants for protein kinase inactivity and have shed light to the biological functions and evolution of this enigmatic subset of the human kinome. Pseudokinases act as signal transducers by bringing together components of signalling networks, as well as allosteric activators of active protein kinases.",
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    Pseudokinases-remnants of evolution or key allosteric regulators? / Zeqiraj, Elton; van Aalten, Daan M. F.

    In: Current Opinion in Structural Biology, Vol. 20, No. 6, 12.2010, p. 772-781.

    Research output: Contribution to journalArticle

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    KW - Acute lymphoblastic leukemia

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    KW - Structural analysis

    KW - Toxoplasma gondii

    KW - Polycythemia vera

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