Triplexed Affinity Reagents to Sample the Mammalian Inositol Pyrophosphate Interactome.
Cell Chem Biol
; 27(8): 1097-1108.e4, 2020 08 20.
Article
em En
| MEDLINE
| ID: mdl-32783964
ABSTRACT
The inositol pyrophosphates (PP-InsPs) are a ubiquitous group of highly phosphorylated eukaryotic messengers. They have been linked to a panoply of central cellular processes, but a detailed understanding of the discrete signaling events is lacking in most cases. To create a more mechanistic picture of PP-InsP signaling, we sought to annotate the mammalian interactome of the most abundant inositol pyrophosphate 5PP-InsP5. To do so, triplexed affinity reagents were developed, in which a metabolically stable PP-InsP analog was immobilized in three different ways. Application of these triplexed reagents to mammalian lysates identified between 300 and 400 putative interacting proteins. These interactomes revealed connections between 5PP-InsP5 and central cellular regulators, such as lipid phosphatases, protein kinases, and GTPases, and identified protein domains commonly targeted by 5PP-InsP5. Both the triplexed affinity reagents, and the proteomic datasets, constitute powerful resources for the community, to launch future investigations into the multiple signaling modalities of inositol pyrophosphates.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Marcadores de Afinidade
/
Monoéster Fosfórico Hidrolases
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GTP Fosfo-Hidrolases
/
Fosfatos de Inositol
Limite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha