In a previous study, we showed that the inositol pyrophosphate diphosphoinositol pentakisphosphate (IP(7)) physiologically phosphorylates mammalian and yeast proteins. We now report that this phosphate transfer reflects pyrophosphorylation. Thus, proteins must be prephosphorylated by ATIP to prime them for IP(7) phosphorylation. IP(7) phosphorylates synthetic phosphopeptides but not if their phosphates have been masked by methylation or pyrophosphorylation. Moreover, IP(7) phosphorylated peptides are more acid-labile and more resistant to phosphatases than ATIP phosphorylated peptides, indicating a different type of phosphate bond. Pyrophosphorylation may represent a novel mode of signaling to proteins.
Bhandari, Rashna, Adolfo Saiardi, Yousef Ahmadibeni, Adele M. Snowman, Adam C. Resnick, Troels Z. Kristiansen, Henrik Molina et al. "Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event." Proceedings of the National Academy of Sciences 104, no. 39 (2007): 15305-15310.
National Academy of Sciences