在Sevenless信号传导路径中,Raf在Ras1的下游运行
B Dickson1, F Sprenger, D Morrison
1Zoologisches Institut, Universität Zürich, Switzerland.
Nature
|December 10, 1992
概括
树Raf血清/三氨酸激酶对于Sevenless (Sev) 途径信号传递至关重要,控制R7细胞命运的决定. 遗传学研究证实,Raf在Ras1的下游和Sina的上游作用于这个发育路径.
科学领域:
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
- 遗传学 是一个遗传学.
背景情况:
- 在Drosophila眼睛发育中的R7细胞命运规范依赖于Sevenless (Sev) 受体氨酸激酶途径.
- 确定的关键信号组件包括Ras1,Sos,Gap1和 sina,它们调解细胞内信号传输.
- 德洛索菲拉拉拉夫的血清/三氨酸激酶,同类于哺乳动物Raf-1,参与受体氨酸激酶信号传递.
研究的目的:
- 调查Drosophila Raf在七无 (Sev) 信号通路中的氨酸/氨酸激酶的作用.
- 为了确定R7细胞命运规范,Raf在细胞内信号传导级联中的位置.
主要方法:
- 在Drosophila melanogaster.中对RAF位点的遗传分析.
- 使用构成性激活Raf蛋白的功能研究.
- 基因表达体验 (genetic epistasis) 是用来确定信号元件的顺序的实验.
主要成果:
- 在R7细胞发育中对Sev活性的反应取决于RAF功能.
- 一种构成性激活的Raf蛋白可以诱导R7细胞的发展,独立于Sev.
- 遗传证据将拉夫置于Ras1的下游和Sina的上游的信号布中.
结论:
- 德洛索菲拉拉拉夫 (Drosophila Raf) 的氨酸/氨酸激酶在Sev介导的R7细胞命运规范途径中发挥着关键作用.
- 拉夫作为一个关键的细胞内信号分子,作用于Ras1的下游和Sina的上游.
- 这些发现阐明了在发育背景下基因受体氨酸激酶信号的分子机制.
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相关概念视频
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
