ATP7B activity is stimulated by PKCɛ in porcine liver

Luiza H. D. Cardoso, Thiago Britto Borges, Adalberto Vieyra, Jennifer Lowe (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    1 Citation (Scopus)

    Abstract

    Copper is necessary for all organisms since it acts as a cofactor in different enzymes, although toxic at high concentrations. ATP7B is one of two copper-transporting ATPases in humans, its vital role being manifested in Wilson disease due to a mutation in the gene that encodes this pump. Our objective has been to determine whether pathways involving protein kinase C (PKC) modulate ATP7B activity. Different isoforms of PKC (a, ?, ?) were found in Golgi-enriched membrane fractions obtained from porcine liver. Cu(I)-ATPase activity was assessed in the presence of different activators and inhibitors of PKC signaling pathways. PMA (10(-8)M), a PKC activator, increased Cu(I)-ATPase activity by 60%, whereas calphostin C and U73122 (PKC and PLC inhibitors, respectively) decreased the activity by 40%. Addition of phosphatase ? decreased activity by 60%, irrespective of pre-incubation with PMA. No changes were detected with 2µM Ca(2+), whereas PMA plus EGTA increased activity. This enhanced activity elicited by PMA decreased with a specific inhibitor of PKC? to levels comparable with those found after phosphatase ? treatment, showing that the ? isoform is essential for activation of the enzyme. This regulatory phosphorylation enhanced Vmax without modifying affinities for ATP and copper. It can be concluded that signaling pathways leading to DAG formation and PKC? activation stimulate the active transport of copper by ATP7B, thus evidencing a central role for this specific kinase-mediated mechanism in hepatic copper handling.
    Original languageEnglish
    Pages (from-to)60-67
    Number of pages8
    JournalInternational Journal of Biochemistry & Cell Biology
    Volume54
    DOIs
    Publication statusPublished - Sep 2014

    Fingerprint Dive into the research topics of 'ATP7B activity is stimulated by PKCɛ in porcine liver'. Together they form a unique fingerprint.

    Cite this