AMPK directly inhibits NDPK through a phosphoserine switch to maintain cellular homeostasis

• DOI: 10.1091/mbc.e11-08-0699
• Publication Date: 2011-11-24T05:55:38Z
• Authors: Rob U. Onyenwoke; Lawrence J. Forsberg; Lucy Liu; Tyisha Williams; Oscar Alzate; Jay E. Brenman
• Keywords: AMP-Activated Protein Kinase; Phosphoserine; Energy homeostasis; Adenosine triphosphate

AMP-activated protein kinase (AMPK) is a key energy sensor that regulates metabolism to maintain cellular balance. AMPK activation has also been proposed mimic benefits of caloric restriction and exercise. Therefore, identifying downstream targets could elucidate new mechanisms for maintaining homeostasis. We identified the phosphotransferase nucleoside diphosphate (NDPK), which maintains pools nucleotides, as direct target through use two-dimensional differential in-gel electrophoresis. Furthermore, we mapped AMPK/NDPK phosphorylation site (serine 120) functionally potent enzymatic “off switch” both in vivo vitro. Because ATP usually most abundant nucleotide, NDPK would normally consume ATP, whereas inhibit conserve energy. It intriguing serine 120 mutated advanced neuroblastoma, suggests mechanism by neuroblastoma can no longer be inhibited AMPK-mediated phosphorylation. This novel placement upstream directly regulating activity widespread implications energy/nucleotide balance, demonstrate increased leads susceptibility deprivation–induced death.