Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event.
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 ATP 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 ATP phosphorylated peptides, indicating a different type of phosphate bond. Pyrophosphorylation may represent a novel mode of signaling to proteins.
Bhandari
Rashna
R
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Saiardi
Adolfo
A
Ahmadibeni
Yousef
Y
Snowman
Adele M
AM
Resnick
Adam C
AC
Kristiansen
Troels Z
TZ
Molina
Henrik
H
Pandey
Akhilesh
A
Werner
J Kent
JK
Juluri
Krishna R
KR
Xu
Yong
Y
Prestwich
Glenn D
GD
Parang
Keykavous
K
Snyder
Solomon H
SH
D000255:Adenosine Triphosphate / Q000737:chemistry*; D000595:Amino Acid Sequence; D011756:Diphosphates / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry; D007295:Inositol Phosphates / Q000737:chemistry*; D008745:Methylation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D011756:Diphosphates; D007295:Inositol Phosphates; D010455:Peptides; D010710:Phosphates; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate