Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 39; pp. 15305 - 15310
• Main Authors: Bhandari, Rashna, Saiardi, Adolfo, Ahmadibeni, Yousef, Snowman, Adele M, Resnick, Adam C, Kristiansen, Troels Z, Molina, Henrik, Pandey, Akhilesh, Werner, J. Kent Jr, Juluri, Krishna R, Xu, Yong, Prestwich, Glenn D, Parang, Keykavous, Snyder, Solomon H
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.09.2007; National Acad Sciences
• Subjects: Adenosine triphosphatase; Adenosine Triphosphate - chemistry; Amino Acid Sequence; Amino acids; Autoradiography; Biochemistry; Biological Sciences; Diphosphates; Diphosphates - chemistry; Escherichia coli - metabolism; Guanosine Triphosphate - chemistry; Inositol Phosphates - chemistry; Inositols; Methylation; Molecular Sequence Data; Peptides; Peptides - chemistry; Phosphatases; Phosphates; Phosphates - chemistry; Phosphors; Phosphorylation; Protein Processing, Post-Translational; Proteins; Saccharomyces cerevisiae - metabolism; Sequence Homology, Amino Acid; Signal Transduction; Yeast extract; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0707338104

In a previous study, we showed that the inositol pyrophosphate diphosphoinositol pentakisphosphate (IP₇) physiologically phosphorylates mammalian and yeast proteins. We now report that this phosphate transfer reflects pyrophosphorylation. Thus, proteins must be prephosphorylated by ATP to prime them for IP₇ phosphorylation. IP₇ phosphorylates synthetic phosphopeptides but not if their phosphates have been masked by methylation or pyrophosphorylation. Moreover, IP₇ phosphorylated peptides are more acid-labile and more resistant to phosphatases than ATP phosphorylated peptides, indicating a different type of phosphate bond. Pyrophosphorylation may represent a novel mode of signaling to proteins.