HIPK2 kinase activity depends on cis-autophosphorylation of its activation loop

Vera V. Saul, Laureano de la Vega, Maja Milanovic, Marcus Krüger, Thomas Braun, Karin Fritz-Wolf, Katja Becker, M. Lienhard Schmitz (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    56 Citations (Scopus)

    Abstract

    The multitude of mechanisms regulating the activity of protein kinases includes phosphorylation of amino acids contained in the activation loop. Here we show that the serine/threonine kinase HIPK2 (homeodomain-interacting protein kinase 2) is heavily modified by autophosphorylation, which occurs by cis-autophosphorylation at the activation loop and by trans-autophosphorylation at other phosphorylation sites. Cis-autophosphorylation of HIPK2 at Y354 and S357 in the activation loop is essential for its kinase function and the binding to substrates and the interaction partner Pin1. HIPK2 activation loop phosphorylation is also required for its biological activity as a regulator of gene expression and cell proliferation. Phosphorylation of HIPK2 at Y354 alone is not sufficient for full HIPK2 activity, which is in marked contrast to some dual-specificity tyrosine-phosphorylated and regulated kinases where tyrosine phosphorylation is absolutely essential. This study shows that differential phosphorylation of HIPK2 provides a mechanism for controlling and specifying the signal output from this kinase.

    Original languageEnglish
    Pages (from-to)27-38
    Number of pages12
    JournalJournal of Molecular Cell Biology
    Volume5
    Issue number1
    Early online date20 Sept 2012
    DOIs
    Publication statusPublished - Feb 2013

    Keywords

    • Amino acid sequence
    • Carrier proteins
    • Cell line
    • Enzyme activation
    • Humans
    • Models, Molecular
    • Molecular sequence data
    • Phosphorylation
    • Protein binding
    • Protein conformation
    • Protein-serine-threonine kinases
    • Sequence alignment
    • Substrate specificity

    Fingerprint

    Dive into the research topics of 'HIPK2 kinase activity depends on cis-autophosphorylation of its activation loop'. Together they form a unique fingerprint.

    Cite this