Role of heparan sulfate as a tissue-specific regulator of FGF-4 and FGF receptor recognition.
Role of heparan sulfate as a tissue-specific regulator of FGF-4 and FGF receptor recognition.
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DOI：
10.1083/jcb.200106075
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发表时间：
2001-11-26
期刊：
影响因子：
--
通讯作者：
Rapraeger AC
中科院分区：
文献类型：
--
作者：
Allen BL;Filla MS;Rapraeger AC
FGF信号传导使用受体酪氨酸激酶，其在细胞表面与FGF和硫酸乙酰肝素（HS）蛋白聚糖形成高亲和力复合物。据推测，这些复合物的组装需要同时识别不同的硫酸化模式内的HS链的FGF和FGF受体（FR），这表明组织特异性的HS合成可以调节FGF信号。为了解决这个问题，FGF-2和FGF-4，以及FR 1-IIIc（FR 1c）和FR 2-IIIc（FR 2c）的细胞外结构域构建体，用于探测胚胎第18天小鼠胚胎中的组织特异性HS。而FGF-2结合HS无处不在，FGF-4表现出有限的模式，不能结合心脏和血管中的HS，不能激活小鼠主动脉内皮细胞中的信号传导。这表明FGF-4寻求一种特定的HS硫酸化模式，与FGF-2不同，FGF-2在大多数血管组织中不表达。此外，尽管FR 2c结合所有FGF-4-HS复合物，但FR 1c在大多数组织以及表达多配体蛋白聚糖-1的Raji-S1细胞中不能结合FGF-4-HS。使用表达FR 1c或FR 2c的BaF 3细胞的增殖测定支持这些结果。这表明FGF和FR识别特定HS硫酸化模式对于FGF信号传导的激活是至关重要的，并且这些模式的合成在胚胎发育期间受到调节。
FGF signaling uses receptor tyrosine kinases that form high-affinity complexes with FGFs and heparan sulfate (HS) proteoglycans at the cell surface. It is hypothesized that assembly of these complexes requires simultaneous recognition of distinct sulfation patterns within the HS chain by FGF and the FGF receptor (FR), suggesting that tissue-specific HS synthesis may regulate FGF signaling. To address this, FGF-2 and FGF-4, and extracellular domain constructs of FR1-IIIc (FR1c) and FR2-IIIc (FR2c), were used to probe for tissue-specific HS in embryonic day 18 mouse embryos. Whereas FGF-2 binds HS ubiquitously, FGF-4 exhibits a restricted pattern, failing to bind HS in the heart and blood vessels and failing to activate signaling in mouse aortic endothelial cells. This suggests that FGF-4 seeks a specific HS sulfation pattern, distinct from that of FGF-2, which is not expressed in most vascular tissues. Additionally, whereas FR2c binds all FGF-4–HS complexes, FR1c fails to bind FGF-4–HS in most tissues, as well as in Raji-S1 cells expressing syndecan-1. Proliferation assays using BaF3 cells expressing either FR1c or FR2c support these results. This suggests that FGF and FR recognition of specific HS sulfation patterns is critical for the activation of FGF signaling, and that synthesis of these patterns is regulated during embryonic development.
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DOI：
10.1083/jcb.128.4.673
发表时间：
1995-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jackson DG;Bell JI;Dickinson R;Timans J;Shields J;Whittle N
通讯作者：
Whittle N
影响因子：
19.6
作者：
Cancilla, B;Ford-Perriss, MD;Bertram, JF
通讯作者：
Bertram, JF
影响因子：
5.6
作者：
GOSPODAROWICZ, D;CHENG, J
通讯作者：
CHENG, J
影响因子：
15.9
作者：
Kleeff, J;Ishiwata, T;Korc, M
通讯作者：
Korc, M
影响因子：
5.3
作者：
DELLIBOVI, P;CURATOLA, AM;BASILICO, C
通讯作者：
BASILICO, C