The identification and characterization of novel PKC epsilon phosphorylation sites provide evidence for functional cross-talk within the PKC superfamily

Joanne Durgan, Angus J. Cameron, Adrian T. Saurin, Sarah Hanrahan, Nick Totty, Robert O. Messing, Peter J. Parker

    Research output: Contribution to journalArticle

    28 Citations (Scopus)

    Abstract

    PKC epsilon (protein kinase C epsilon) is a phospholipid-dependent serine/threonine kinase that has been implicated in a broad array of cellular processes, including proliferation, survival, migration, invasion and transformation. Here we demonstrate that, in vitro, PKC epsilon undergoes autophosphorylation at three novel sites, Ser(234), Ser(316) and Ser(368), each of which is unique to this PKC isoform and is evolutionarily conserved. We show that these sites are phosphorylated over a range of mammalian cell lines in response to a number of different stimuli. Unexpectedly, we find that, in a cellular context, these phosphorylation events can be mediated in-trans by cPKC (classical PKC) isoforms. The functional significance of this cross-talk is illustrated through the observation that the cPKC-mediated phosphorylation of PKC epsilon at residue Set(368) controls an established PKC epsilon scaffold interaction. Thus our current findings identify three new phosphorylation sites that contribute to the isoform-specific function of PKC epsilon and highlight a novel and direct means of cross-talk between different members of the PKC superfamily.

    Original languageEnglish
    Pages (from-to)319-331
    Number of pages13
    JournalBiochemical Journal
    Volume411
    DOIs
    Publication statusPublished - 15 Apr 2008

    Keywords

    • activation marker
    • DOWN-REGULATION
    • CELLS
    • protein kinase C epsilon (PKC epsilon)
    • CRYSTAL-STRUCTURE
    • CATALYTIC DOMAIN
    • ACTIVATION
    • APOPTOSIS
    • PROTEIN-KINASE-C
    • THYROID-CANCER
    • AUTOPHOSPHORYLATION
    • ALPHA
    • phosphorylation
    • chemical genetics
    • T-loop

    Cite this

    Durgan, Joanne ; Cameron, Angus J. ; Saurin, Adrian T. ; Hanrahan, Sarah ; Totty, Nick ; Messing, Robert O. ; Parker, Peter J. / The identification and characterization of novel PKC epsilon phosphorylation sites provide evidence for functional cross-talk within the PKC superfamily. In: Biochemical Journal. 2008 ; Vol. 411. pp. 319-331.
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    The identification and characterization of novel PKC epsilon phosphorylation sites provide evidence for functional cross-talk within the PKC superfamily. / Durgan, Joanne; Cameron, Angus J.; Saurin, Adrian T.; Hanrahan, Sarah; Totty, Nick; Messing, Robert O.; Parker, Peter J.

    In: Biochemical Journal, Vol. 411, 15.04.2008, p. 319-331.

    Research output: Contribution to journalArticle

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    AU - Durgan, Joanne

    AU - Cameron, Angus J.

    AU - Saurin, Adrian T.

    AU - Hanrahan, Sarah

    AU - Totty, Nick

    AU - Messing, Robert O.

    AU - Parker, Peter J.

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    N2 - PKC epsilon (protein kinase C epsilon) is a phospholipid-dependent serine/threonine kinase that has been implicated in a broad array of cellular processes, including proliferation, survival, migration, invasion and transformation. Here we demonstrate that, in vitro, PKC epsilon undergoes autophosphorylation at three novel sites, Ser(234), Ser(316) and Ser(368), each of which is unique to this PKC isoform and is evolutionarily conserved. We show that these sites are phosphorylated over a range of mammalian cell lines in response to a number of different stimuli. Unexpectedly, we find that, in a cellular context, these phosphorylation events can be mediated in-trans by cPKC (classical PKC) isoforms. The functional significance of this cross-talk is illustrated through the observation that the cPKC-mediated phosphorylation of PKC epsilon at residue Set(368) controls an established PKC epsilon scaffold interaction. Thus our current findings identify three new phosphorylation sites that contribute to the isoform-specific function of PKC epsilon and highlight a novel and direct means of cross-talk between different members of the PKC superfamily.

    AB - PKC epsilon (protein kinase C epsilon) is a phospholipid-dependent serine/threonine kinase that has been implicated in a broad array of cellular processes, including proliferation, survival, migration, invasion and transformation. Here we demonstrate that, in vitro, PKC epsilon undergoes autophosphorylation at three novel sites, Ser(234), Ser(316) and Ser(368), each of which is unique to this PKC isoform and is evolutionarily conserved. We show that these sites are phosphorylated over a range of mammalian cell lines in response to a number of different stimuli. Unexpectedly, we find that, in a cellular context, these phosphorylation events can be mediated in-trans by cPKC (classical PKC) isoforms. The functional significance of this cross-talk is illustrated through the observation that the cPKC-mediated phosphorylation of PKC epsilon at residue Set(368) controls an established PKC epsilon scaffold interaction. Thus our current findings identify three new phosphorylation sites that contribute to the isoform-specific function of PKC epsilon and highlight a novel and direct means of cross-talk between different members of the PKC superfamily.

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