| First Author | Polykratis A | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 4 | Pages | 1539-1543 |
| PubMed ID | 25015821 | Mgi Jnum | J:241205 |
| Mgi Id | MGI:5897979 | Doi | 10.4049/jimmunol.1400590 |
| Citation | Polykratis A, et al. (2014) Cutting edge: RIPK1 Kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo. J Immunol 193(4):1539-43 |
| abstractText | The serine/threonine kinase RIPK1 is recruited to TNFR1 to mediate proinflammatory signaling and to regulate TNF-induced cell death. A RIPK1 deficiency results in perinatal lethality, impaired NFkappaB and MAPK signaling, and sensitivity to TNF-induced apoptosis. Chemical inhibitor and in vitro-reconstitution studies suggested that RIPK1 displays distinct kinase activity-dependent and -independent functions. To determine the contribution of RIPK1 kinase to inflammation in vivo, we generated knock-in mice endogenously expressing catalytically inactive RIPK1 D138N. Unlike Ripk1(-/-) mice, which die shortly after birth, Ripk1(D138N/D138N) mice are viable. Cells expressing RIPK1 D138N are resistant to TNF- and polyinosinic-polycytidylic acid-induced necroptosis in vitro, and Ripk1(D138N/D138N) mice are protected from TNF-induced shock in vivo. Moreover, Ripk1(D138N/D138N) mice fail to control vaccinia virus replication in vivo. This study provides genetic evidence that the kinase activity of RIPK1 is not required for survival but is essential for TNF-, TRIF-, and viral-initiated necroptosis. |
