Fibroblast growth factor homologous factors are intracellular signaling proteins
Fibroblast growth factor homologous factors are intracellular signaling proteins
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DOI：
10.1016/s0960-9822(01)00232-9
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发表时间：
2001-05-15
期刊：
影响因子：
9.2
通讯作者：
Goldfarb, M
中科院分区：
文献类型：
--
作者：
Schoorlemmer, J;Goldfarb, M
成纤维细胞生长因子（FGF）通过与细胞表面受体的细胞外结构域结合，触发受体酪氨酸磷酸化和信号转导，介导细胞生长、分化、迁移和形态发生[1-5]。FGF同源因子（FHF）由于其与FGF的序列相似性而在脊椎动物DNA序列数据库中被发现[3，6，7]，但FHF作用的机制尚未报道。我们在这里表明，FHF-1与脑和特定细胞系中的MAP激酶（MAPK）支架蛋白Islet-Brain-2（IB 2）[8]相关。FHF/IB 2相互作用是高度特异性的，因为FHF不结合相关的支架蛋白IB 1（JIP-1b）[9，10]，FGF-1也不能结合IB 2。我们进一步表明，FHF使IB 2能够在转染细胞中募集特异性MAPK，并且我们的数据表明，支架IB 1和IB 2具有不同的MAPK特异性。因此，FHF是组织特异性蛋白激酶信号传导模块的细胞内组分。
Fibroblast growth factors (FGFs) mediate cell growth, differentiation, migration, and morphogenesis by binding to the extracellular domain of cell surface receptors, triggering receptor tyrosine phosphorylation and signal transduction [1-5]. FGF homologous factors (FHFs) were discovered within vertebrate DNA sequence databases by virtue of their sequence similarity to FGFs [3, 6, 7], but the mechanism of FHF action has not been reported. We show here that FHF-1 is associated with the MAP kinase (MAPK) scaffold protein Islet-Brain-2 (IB2) [8] in the brain and in specific cell lines. FHF/IB2 interaction is highly specific, as FHFs do not bind to the related scaffold protein IB1(JIP-1b) [9, 10], nor can FGF-1 bind to IB2. We further show that FHFs enable IB2 to recruit a specific MAPK in transfected cells, and our data suggest that the scaffolds IB1 and IB2 have different MAPK specificities. Hence, FHFs are intracellular components of a tissue-specific protein kinase signaling module.