A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation.
A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation.
复制标题
DOI：
10.1083/jcb.200302075
复制
发表时间：
2003-06-23
期刊：
影响因子：
--
通讯作者：
Basilico C
中科院分区：
文献类型：
--
作者：
Dailey L;Laplantine E;Priore R;Basilico C
成纤维细胞生长因子受体3(FGFR3)的激活突变通过影响软骨细胞的增殖和分化而导致几种人类侏儒症。通过对成纤维细胞生长因子处理的大鼠软骨肉瘤软骨细胞进行基因芯片和生化分析，我们发现成纤维细胞生长因子通过启动多条途径抑制软骨细胞的增殖，导致抑制增殖功能的诱导和促生长分子的下调。视网膜母细胞瘤蛋白(PRB)p107的快速去磷酸化和抑制E2F靶基因的一种不依赖于细胞周期蛋白E-CDK抑制的机制是生长停滞的开始。相反，pRb和p130的低磷酸化发生在第一次检测到生长停滞之后，并可能有助于其维持。重要的是，我们还发现了一些基因表达的变化，表明成纤维细胞生长因子促进肥大分化的许多方面，这一观点得到了对表达活化形式的FGFR3的小鼠生长板的原位分析的支持。因此，在发育中的生长板中，成纤维细胞生长因子可能协调软骨细胞的分化和生长停止。
Activating mutations in FGF receptor 3 (FGFR3) cause several human dwarfism syndromes by affecting both chondrocyte proliferation and differentiation. Using microarray and biochemical analyses of FGF-treated rat chondrosarcoma chondrocytes, we show that FGF inhibits chondrocyte proliferation by initiating multiple pathways that result in the induction of antiproliferative functions and the down-regulation of growth-promoting molecules. The initiation of growth arrest is characterized by the rapid dephosphorylation of the retinoblastoma protein (pRb) p107 and repression of a subset of E2F target genes by a mechanism that is independent of cyclin E–Cdk inhibition. In contrast, hypophosphorylation of pRb and p130 occur after growth arrest is first detected, and may contribute to its maintenance. Importantly, we also find a number of gene expression changes indicating that FGF promotes many aspects of hypertrophic differentiation, a notion supported by in situ analysis of developing growth plates from mice expressing an activated form of FGFR3. Thus, FGF may coordinate the onset of differentiation with chondrocyte growth arrest in the developing growth plate.
登录
查看更多内容
影响因子：
4.8
作者：
Aikawa, T;Segre, GV;Lee, K
通讯作者：
Lee, K
影响因子：
15.9
作者：
Chen, L;Adar, R;Deng, CX
通讯作者：
Deng, CX
影响因子：
3.5
作者：
Li, CL;Chen, L;Deng, CX
通讯作者：
Deng, CX
影响因子：
4.8
作者：
Shen, M;Yoshida, E;Kato, Y
通讯作者：
Kato, Y
影响因子：
64.8
作者：
BRUGAROLAS, J;CHANDRASEKARAN, C;HANNON, GJ
通讯作者：
HANNON, GJ