一个生长因子受体上的明显的类胺与特定的分子结合,这些分子介导着不同的信号通路
W J Fantl1, J A Escobedo, G A Martin
1Howard Hughes Medical Institute, University of California, San Francisco 94143.
Cell
|May 1, 1992
概括
血小板衍生生长因子 (PDGF) 受体在不同的部位结合了GTPase激活蛋白 (GAP) 和酸丁醇3-激酶 (PI3-激酶). 这些相互作用对于PDGF刺激的DNA合成至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 血小板衍生生长因子 (PDGF) 受体是细胞生长和增殖的关键调节者.
- 它与细胞内信号蛋白相互作用,如GTPase激活蛋白 (GAP) 和酸丁醇3-激酶 (PI3-激酶),它们含有SH2域.
研究的目的:
- 为了确定PI3-酶和GAP的PDGF受体上的特定结合位.
- 阐明这些相互作用在PDGF介导信号传输中的功能意义.
主要方法:
- 使用含胺的酸盐,代表PDGF受体序列,以竞争性抑制PI3-激酶和GAP结合.
- 引入了PDGF受体上已识别的结合部位的点突变.
主要成果:
- PI3-激酶与PDGF受体上的特定序列基因内两个不同的铁氨酸残留物结合.
- 这些PI3-激酶结合位点的突变取消了PI3-激酶关联,并损害了PDGF刺激的DNA合成.
- GAP结合部位的突变破坏了GAP关联和酸化,但没有影响PI3-激酶结合或显著影响DNA合成.
结论:
- 在PDGF受体上,GAP和PI3-激酶结合到单独的含胺的序列基因.
- PI3-激酶结合部位对于调解PDGF刺激的DNA合成至关重要,而GAP结合部位的作用较小.
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