RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation

Marina S. Vivarelli; Douglas McDonald; Mendy Miller; Nicole Cusson; Michelle Kelliher; Raif S. Geha

doi:10.1084/jem.20040446

RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation

Marina S. Vivarelli, Douglas McDonald, Mendy Miller, Nicole Cusson, Michelle Kelliher, Raif S. Geha

Ospedale Pediatrico Bambino Gesu

Research output: Contribution to journal › Article › peer-review

Abstract

Receptor-interacting protein (RIP) has been reported to associate with tumor necrosis-associated factor (TRAF)2 and TRAF6. Since TRAF2 and TRAF6 play important roles in CD40 signaling and TRAF6 plays an important role in TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4. Splenocytes from RIP^-/- mice proliferated and underwent isotype switching normally in response to anti-CD40-IL-4 but completely failed to do so in response to LPS-IL-4. However, they normally up-regulated TNF-α and IL-6 gene expression and CD54 and CD86 surface expression after LPS stimulation. RIP^-/- splenocytes exhibited increased apoptosis and impaired Akt phosphorylation after LPS stimulation. These results suggest that RIP is essential for cell survival after TLR4 signaling and links TLR4 to the phosphatidylinositol 3 kinase-Akt pathway.

Original language	English
Pages (from-to)	399-404
Number of pages	6
Journal	Journal of Experimental Medicine
Volume	200
Issue number	3
DOIs	https://doi.org/10.1084/jem.20040446
Publication status	Published - Aug 2 2004

Keywords

IκB
IL-6
NFκB
p38 MAP kinase
TNF-α

ASJC Scopus subject areas

Immunology

Access to Document

10.1084/jem.20040446

Fingerprint Dive into the research topics of 'RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation'. Together they form a unique fingerprint.

Cite this

@article{35f7ee0a32314855ad3e4baa1d3d71ed,

title = "RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation",

abstract = "Receptor-interacting protein (RIP) has been reported to associate with tumor necrosis-associated factor (TRAF)2 and TRAF6. Since TRAF2 and TRAF6 play important roles in CD40 signaling and TRAF6 plays an important role in TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4. Splenocytes from RIP-/- mice proliferated and underwent isotype switching normally in response to anti-CD40-IL-4 but completely failed to do so in response to LPS-IL-4. However, they normally up-regulated TNF-α and IL-6 gene expression and CD54 and CD86 surface expression after LPS stimulation. RIP-/- splenocytes exhibited increased apoptosis and impaired Akt phosphorylation after LPS stimulation. These results suggest that RIP is essential for cell survival after TLR4 signaling and links TLR4 to the phosphatidylinositol 3 kinase-Akt pathway.",

keywords = "IκB, IL-6, NFκB, p38 MAP kinase, TNF-α",

author = "Vivarelli, {Marina S.} and Douglas McDonald and Mendy Miller and Nicole Cusson and Michelle Kelliher and Geha, {Raif S.}",

year = "2004",

month = aug,

day = "2",

doi = "10.1084/jem.20040446",

language = "English",

volume = "200",

pages = "399--404",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "3",

}

TY - JOUR

T1 - RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation

AU - Vivarelli, Marina S.

AU - McDonald, Douglas

AU - Miller, Mendy

AU - Cusson, Nicole

AU - Kelliher, Michelle

AU - Geha, Raif S.

PY - 2004/8/2

Y1 - 2004/8/2

N2 - Receptor-interacting protein (RIP) has been reported to associate with tumor necrosis-associated factor (TRAF)2 and TRAF6. Since TRAF2 and TRAF6 play important roles in CD40 signaling and TRAF6 plays an important role in TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4. Splenocytes from RIP-/- mice proliferated and underwent isotype switching normally in response to anti-CD40-IL-4 but completely failed to do so in response to LPS-IL-4. However, they normally up-regulated TNF-α and IL-6 gene expression and CD54 and CD86 surface expression after LPS stimulation. RIP-/- splenocytes exhibited increased apoptosis and impaired Akt phosphorylation after LPS stimulation. These results suggest that RIP is essential for cell survival after TLR4 signaling and links TLR4 to the phosphatidylinositol 3 kinase-Akt pathway.

AB - Receptor-interacting protein (RIP) has been reported to associate with tumor necrosis-associated factor (TRAF)2 and TRAF6. Since TRAF2 and TRAF6 play important roles in CD40 signaling and TRAF6 plays an important role in TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4. Splenocytes from RIP-/- mice proliferated and underwent isotype switching normally in response to anti-CD40-IL-4 but completely failed to do so in response to LPS-IL-4. However, they normally up-regulated TNF-α and IL-6 gene expression and CD54 and CD86 surface expression after LPS stimulation. RIP-/- splenocytes exhibited increased apoptosis and impaired Akt phosphorylation after LPS stimulation. These results suggest that RIP is essential for cell survival after TLR4 signaling and links TLR4 to the phosphatidylinositol 3 kinase-Akt pathway.

KW - IκB

KW - IL-6

KW - NFκB

KW - p38 MAP kinase

KW - TNF-α

UR - http://www.scopus.com/inward/record.url?scp=3543097542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3543097542&partnerID=8YFLogxK

U2 - 10.1084/jem.20040446

DO - 10.1084/jem.20040446

M3 - Article

C2 - 15280422

AN - SCOPUS:3543097542

VL - 200

SP - 399

EP - 404

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -