N-Glycosylation Regulates Fibroblast Growth Factor Receptor/EGL-15 Activity in Caenorhabditis elegans in Vivo*
N-Glycosylation Regulates Fibroblast Growth Factor Receptor/EGL-15 Activity in Caenorhabditis elegans in Vivo*
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N-糖基化调节秀丽隐杆线虫体内成纤维细胞生长因子受体/EGL-15 活性*
DOI：
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发表时间：
2009
影响因子：
4.8
通讯作者：
T. Kinnunen
中科院分区：
文献类型：
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作者：
U. Polanska;L. Duchesne;Janet C. Harries;D. Fernig;T. Kinnunen
成纤维细胞生长因子（FGFs）对细胞功能的调节通常是通过酪氨酸激酶受体（FGFR）和硫酸肝素蛋白聚糖共受体的双受体系统发生的。人类FGFR中一些一致的n -糖基化位点的突变可导致骨骼疾病和颅缝闭综合征，体外生物物理学研究表明，FGFR的n -糖基化改变了配体和硫酸肝素的结合特性。秀丽隐杆线虫进化上保守的FGFR信号系统已被用于评估n -糖基化在体内调节FGFR信号传导中的作用。线虫FGF受体EGL-15在体内被n -糖基化，特定一致n -糖基化位点的遗传替代导致液体稳态维持和性肌分化的缺陷，这两种表型先前都与EGL-15信号过度活跃相关。这些表型分别被EGL-15下游信号成分的低活性突变或磷脂酰肌醇3-激酶途径的激活突变所抑制。结果表明，n -聚糖在体内负调控FGFR活性，支持了人类FGFR中n -糖基化位点突变可能导致受体不适当激活的观点。
The regulation of cell function by fibroblast growth factors (FGFs) classically occurs through a dual receptor system of a tyrosine kinase receptor (FGFR) and a heparan sulfate proteoglycan co-receptor. Mutations in some consensus N-glycosylation sites in human FGFR result in skeletal disorders and craniosynostosis syndromes, and biophysical studies in vitro suggest that N-glycosylation of FGFR alters ligand and heparan sulfate binding properties. The evolutionarily conserved FGFR signaling system of Caenorhabditis elegans has been used to assess the role of N-glycosylation in the regulation of FGFR signaling in vivo. The C. elegans FGF receptor, EGL-15, is N-glycosylated in vivo, and genetic substitution of specific consensus N-glycosylation sites leads to defects in the maintenance of fluid homeostasis and differentiation of sex muscles, both of which are phenotypes previously associated with hyperactive EGL-15 signaling. These phenotypes are suppressed by hypoactive mutations in EGL-15 downstream signaling components or activating mutations in the phosphatidylinositol 3-kinase pathway, respectively. The results show that N-glycans negatively regulate FGFR activity in vivo supporting the notion that mutation of N-glycosylation sites in human FGFR may lead to inappropriate activation of the receptor.
吸引和排斥迁移的性成肌细胞需要不同亚型的线虫 FGF 受体。
影响因子：
2.7
作者：
Lo,Te-Wen;Branda,CatherineS;Huang,Peng;Sasson,IsaacE;Goodman,SJay;Stern,MichaelJ
通讯作者：
Stern,MichaelJ
影响因子：
9.8
作者：
White, KE;Cabral, JM;Econs, MJ
通讯作者：
Econs, MJ
影响因子：
11.4
作者：
MELLO, CC;KRAMER, JM;AMBROS, V
通讯作者：
AMBROS, V