The NF1 tumor suppressor gene encodes for neurofibromin, a RAS GTPase-activating protein (GAP) that promotes the conversion of an active RAS-GTP-bound form to an inactive RAS-GDP form and functions to negatively regulate the activity of RAS effectors, including the RAF–MEK–ERK signaling pathway (Cichowski and Jacks 2001; Zhu et al. 2001).

2008年10月31日 · We show that the learning deficits of Nf1+/− mice are due to increases in ERK activation that lead to higher levels of synapsin I phosphorylation, greater GABA release, and consequently to LTP and learning deficits.

2020年11月11日 · Here, we have sought targets offering a more narrow inhibition of ERK activation downstream of NF1 loss in the skeleton, finding that MEKK2 is a novel component of a noncanonical ERK pathway...

2012年8月17日 · Nf1-deficient brains exhibit enlarged corpus callosum, a structural defect linked to severe learning deficits in NF1 patients. Strikingly, these NF1-associated developmental defects are rescued by transient treatment with an MEK/ERK inhibitor during neonatal stages.

2014年11月1日 · The NF1 gene encodes for neurofibromin, a RAS GTPase-activating protein, and thus negatively regulates the RAS signaling pathway. Here, using mouse models to direct conditional NF1 ablation in either embryonic cerebellar progenitors or neonatal GNPs, we show that neurofibromin is required for appropriate development of cerebellar folia layering ...

2009年11月22日 · These results confirm a key role for Ras in shaping ERK response kinetics and suggest that NF1 is a crucial Ras regulator, in PC12 cells. Importantly, NF1 downregulation enabled EGF to...

神经纤维瘤 （NF1） 是 RAS 信号传导的负调节因子，在癌症中经常发生突变。 NF1 突变黑色素瘤是一种高度恶性的肿瘤，缺乏靶向治疗。 在这里，我们对患者来源的模型和同基因细胞系使用生化和药理学测定来确定潜在的药理学靶点，揭示 NF1 缺失黑色素瘤依赖于 RAS 激活，并且 MEK 抑制减轻了 ERK 依赖性负反馈，增加了 RAS 信号传导。 用 avutometinib 抑制 MEK 消除了 ERK 信号传导的适应性反弹，但抗肿瘤作用有限。 然而，同时抑制 MEK 和 SOS1 消除了 ERK 活 …

NOTCH, ERK, and SHH signaling respectively control the fate determination of cortical glia and olfactory bulb interneurons. ... Y. Wang et al., ERK inhibition rescues defects in fate specification of Nf1-deficient neural progenitors and brain abnormalities. Cell 150, 816–830 (2012). Crossref. PubMed. Google Scholar. Information & Authors ...

2022年12月15日 · 最近的研究表明，抑制ras下游丝裂原活化蛋白激酶（mek）活性可使nf1相关丛状神经纤维瘤（pn）缩小，司美替尼因此获批用于治疗有症状、不可手术的nf1相关pn儿童患者，这是美国、欧盟和其他国家首个获批该适应症的药物。

2015年9月14日 · Oncogenic mutations of NRAS, KRAS, BRAF, MEK1, and NF1 drive the ERK-dependent growth of many human cancers. These mutations activate both downstream signaling and potent negative feedback, as evidenced by reactivation of upstream and parallel components of the pathway in cells exposed to MEK or RAF inhibitors ( Corcoran et al., 2012; Lito et ...