Immunity. 1996 Apr;4(4):387-96.

TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex.External

Hsu, H., Huang, J., Shu, H. B., Baichwal, V., Goeddel, D. V.,
--- - Tularik, Incorporated, South San Francisco, California 94080, USA.
The death domain of tumor necrosis factor (TNF) receptor-1 (TNFR1) triggers distinct signaling pathways leading to apoptosis and NF-kappa B activation through its interaction with the death domain protein TRADD. Here, we show that TRADD interacts strongly with RIP, another death domain protein that was shown previously to associate with Fas antigen. We also show that RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process. Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis. However, expression of the death domain of RIP Induces apoptosis, but potently inhibits NF-kappa B activation by TNF. These results suggest that distinct domains of RIP participate in the TNF signaling cascades leading to apoptosis and NF-kappa B activation.
PMID: 8612133External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD RIP Link TNFR1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 8612133
DD RIP Link TNFR1 Co-immunoprecipitation HEK293 Not specified Full length Not specified Not specified 8612133
DD RIP Link TNFR1 Co-immunoprecipitation HEK293 Not specified 240-671 Not specified Not specified 8612133
DD RIP Link TNFR1 Co-immunoprecipitation HEK293 Not specified 559-671 Not specified Not specified 8612133
DD RIP Link TRADD Co-immunoprecipitation HEK293 Not specified Full length Not specified Not specified 8612133
DD RIP Link TRADD Co-immunoprecipitation HEK293 Not specified 240-671 Not specified Not specified 8612133
DD RIP Link TRADD Co-immunoprecipitation HEK293 Not specified 559-671 Not specified Not specified 8612133
DD TNFR1 Link TRADD Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 8612133
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
DD RIP Link TNFR1 Data not shown Apoptosis (DISC) 8612133
(Link: click this icon to show interactions only between the two corresponding DDs)