FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase

被引：348

作者：

AdamKlages, S

Adam, D

Wiegmann, K

Struve, S

Kolanus, W

SchneiderMergener, J

Kronke, M

机构：

[1] UNIV MUNICH,GENZENTRUM,MOL BIOL LAB,D-81375 MUNICH,GERMANY

[2] UNIV KLINIKUM CHARITE,INST MED IMMUNOL,D-10117 BERLIN,GERMANY

来源：

CELL | 1996年 / 86卷 / 06期

关键词：

D O I：

10.1016/S0092-8674(00)80169-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The initiation of intracellular signaling events through the 55 kDa tumor necrosis factor-receptor (TNF-R55) appears to depend on protein intermediates that interact with specific cytoplasmic domains of TNF-R55. By combined use of the yeast interaction trap system and a peptide scanning library, the novel WD-repeat protein FAN has been identified, which specifically binds to a cytoplasmic nine amino acid binding motif of TNF-R55. This region has been previously recognized as a distinct functional domain that is both required and sufficient for the activation of neutral sphingomyelinase (N-SMase). Overexpression of full-length FAN enhanced N-SMase activity in TNF-treated cells, while truncated mutants of FAN produced dominant negative effects. The data suggest that FAN regulates ceramide production by N-SMase, which is a crucial step in TNF signaling.

引用

页码：937 / 947

页数：11

共 63 条

[41] THE ANCIENT REGULATORY-PROTEIN FAMILY OF WD-REPEAT PROTEINS [J].