Regulation of brain-type creatine kinase by AMP-activated protein kinase: Interaction, phosphorylation and ER localization

Sacnicte Ramirez Rios, Frederic Lamarche, Cecile Cottet-Rousselle, Anna Klaus, Roland Tuerk, Ramon Thali, Yolanda Auchli, Rene Brunisholz, Dietbert Neumann, Luc Barret, Malgorzata Tokarska-Schlattner, Uwe Schlattner*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review


    AMP-activated protein kinase (AMPK) and cytosolic brain-type creatine kinase (BCK) cooperate under energy stress to compensate for loss of adenosine triphosphate (ATP) by either stimulating ATP-generating and inhibiting ATP-consuming pathways, or by direct ATP regeneration from phosphocreatine, respectively. Here we report on AMPK-dependent phosphorylation of BCK from different species identified by in vitro screening for AMPK substrates in mouse brain. Mass spectrometry, protein sequencing, and site-directed mutagenesis identified Ser6 as a relevant residue with one site phosphorylated per BCK dimer. Yeast two-hybrid analysis revealed interaction of active AMPK specifically with non-phosphorylated BCK. Pharmacological activation of AMPK mimicking energy stress led to BCK phosphorylation in astrocytes and fibroblasts, as evidenced with a highly specific phospho-Ser6 antibody. BCK phosphorylation at Ser6 did not affect its enzymatic activity, but led to the appearance of the phosphorylated enzyme at the endoplasmic reticulum (ER), close to the ER calcium pump, a location known for muscle-type cytosolic creatine kinase (CK) to support Ca?-pumping.
    Original languageEnglish
    Pages (from-to)1271-1283
    JournalBiochimica et Biophysica Acta-bioenergetics
    Issue number8
    Publication statusPublished - Aug 2014


    • Protein kinase
    • Creatine kinase
    • Endoplasmic reticulum
    • Energy homeostasis
    • Protein phospholylation
    • Subcellular localization

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