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The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-?B activation by disturbing the interaction of XIAP with RIP2.

ABSTRACT: SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-?B activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-?B activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-?B signaling.

SUBMITTER: Conde C

PROVIDER: S-EPMC3398883 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-κB activation by disturbing the interaction of XIAP with RIP2.

Condé Claude C Rambout Xavier X Lebrun Marielle M Lecat Aurore A Di Valentin Emmanuel E Dequiedt Franck F Piette Jacques J Gloire Geoffrey G Legrand Sylvie S

PloS one 20120717 7

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-κB activation in macrophages. This negative regulation relies ...[more]

PMID: 22815893

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