FGFR3融合在癌症中的信号传导
中文名称
通路描述
近年来，FGFR3的反复融合在多种癌症中被发现，包括胶质母细胞瘤和肺、膀胱癌等（Singh et al, 2012; Parker et al, 2013; Williams et al, 2013; Wu et al, 2013; Capelletti et al, 2014; Yuan et al, 2014; Wang et al, 2014; Carneiro et al, 2015; 综述 Parker et al, 2014）。FGFR3最常见的融合伙伴是TACC3（转化酸性螺旋结构蛋白3），一种参与有丝纺锤体组装和染色体分离的蛋白质（Lin et al, 2010; Burgess et al, 2015）。FGFR3融合具有持续活性，并能通过融合伙伴提供的二聚化结构域以无配体依赖的方式形成寡聚体（Singh et al, 2012; Williams et al, 2013; Parker et al, 2013; 综述 Parker et al, 2014）。转化和增殖似乎通过激活ERK和AKT信号通路得到促进。相比之下，PLC gamma信号传导在FGFR3融合下游未被刺激，因为融合中不存在PLC gamma的结合位点。FGFR3融合对蛋白激酶抑制剂敏感，表明其作为治疗靶点的潜力（Singh et al, 2012; Williams et al, 2013; Wu et al, 2013; 综述 Parker et al, 2014）。
英文描述
Constitutive Signaling by AKT1 E17K in Cancer While AKT1 gene copy number, expression level and phosphorylation are often increased in cancer, only one low frequency point mutation has been repeatedly reported in cancer and functionally studied. This mutation represents a substitution of a glutamic acid residue with lysine at position 17 of AKT1, and acts by enabling AKT1 to bind PIP2. PIP2-bound AKT1 is phosphorylated by TORC2 complex and by PDPK1 that is always present at the plasma membrane, due to low affinity for PIP2. Therefore, E17K substitution abrogates the need for PI3K in AKT1 activation (Carpten et al. 2007, Landgraf et al. 2008).
所含基因
26 个基因