Impaired neutral sphingomyelinase activation and cutaneous barrier repair in FAN-deficient mice

被引：67

作者：

Kreder, D

Krut, O

Adam-Klages, S

Wiegmann, K

Scherer, G

Plitz, T

Jensen, JM

Proksch, E

Steinmann, J

Pfeffer, K

Krönke, M

机构：

[1] Univ Kiel, Inst Immunol, D-24105 Kiel, Germany

[2] Univ Kiel, Dept Dermatol, D-24105 Kiel, Germany

[3] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-8000 Munich, Germany

来源：

EMBO JOURNAL | 1999年 / 18卷 / 09期

关键词：

Beige; Chediak-Higashi syndrome; ERK; FAN; neutral sphingomyelinase;

D O I：

10.1093/emboj/18.9.2472

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 WD-40 repeat protein FAN binds to a distinct domain of the p55 receptor for tumor necrosis factor (TNF) and signals the activation of neutral sphingomyelinase (N-SMase). To analyze the physiological role of FAN in vivo, we generated FAN-deficient mice by targeted gene disruption. Mice lacking a functional FAN protein do not show any overt phenotypic abnormalities; in particular, the architecture and cellular composition of lymphoid organs appeared to be unaltered. An essential role of FAN in the TNF-induced activation of N-SMase was demonstrated using thymocytes from FAN knockout mice. Activation of extracellular signal-regulated kinases in response to TNF treatment, however, was not impaired by the absence of the FAN protein. FAN-deficient mice show delayed kinetics of recovery after cutaneous barrier disruption suggesting a physiological role of FAN in epidermal barrier repair. Although FAN exhibits striking structural homologies with the CHS/Beige proteins, FAN-deficient mice did not reproduce the phenotype of beige mice.

引用

页码：2472 / 2479

页数：8

共 31 条

[1] A novel cytoplasmic domain of the p55 tumor necrosis factor receptor initiates the neutral sphingomyelinase pathway [J].