PI3K-Akt信号通路是细胞中一个关键的信号传导网络，它可被多种细胞刺激或毒性损伤所激活，并在调控转录、翻译、增殖、生长和存活等基本细胞功能中扮演重要角色。 当生长因子与细胞膜上的 受体酪氨酸激酶 （RTK）或 G蛋白偶联受体 （GPCR）结合时，它们会分别刺激Ia和Ib类PI3K同工酶。 这些被激活的PI3K在细胞膜上催化磷脂酰肌醇，产生第二信使分子—— 磷脂酰肌醇-3,4, 5-三磷酸酯 （PIP3）。 PIP3随后作为关键分子，帮助激活Akt（蛋白激酶B）。 一旦Akt被激活， …

磷脂酰肌醇3-激酶 (PI3Ks)蛋白家族参与细胞存活、生长、代谢和血糖稳态等多种细胞功能的调控。 PI3K激酶活性升高通常与多种癌症相关。顾名思义，PI3Ks磷酸化磷脂酰肌醇PI（一种膜磷脂）肌醇环的第3位碳原子。PI在细胞膜组分中所占比例较小，比磷脂酰胆碱、磷脂酰乙醇胺和磷脂酰丝氨酸含量少, 但在脑细胞膜中，含量较为丰富，达磷脂总量的10%。 PI的肌醇环上有5个可被磷酸化的位点，多种激酶可磷酸化PI肌醇环上的第4及第5位点，因而通常在这两个位点之一或两 …

Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.

2023年11月15日 · Short APC mutant CRC cells exhibited high/intermediate sensitivities to tankyrase inhibitors in vitro and in vivo. Active β-catenin levels correlated with inhibitor sensitivity in both short and...

This concept has been demonstrated by the mutual exclusivity found between APC and beta-catenin mutations (Morin et al. 1997; Sparks et al. 1998) or KRAS and BRAF mutations (Davies et al. 2002; Rajagopalan et al. 2002). The work of Saal et al. indicates that this notion is also true for the PI3K pathway (Saal et al. 2005). In this study, the ...

In human CRCs, PIK3CA mutations most commonly occur concomitantly with loss of Adenomatous Polyposis Coli (APC). Here treatment strategies are investigated that target the PI3K pathway in colon cancers with mutations in APC and PIK3CA.

Phosphatidylinositol 3-kinase (PI3K) is lipid kinases that regulate diverse cellular processes including proliferation, adhesion, survival, and motility. Dysregulated PI3K pathway signaling occurs in one-third of human tumors. Aberrantly activated PI3K signaling also confers sensitivity and resistance to conventional therapies.

In human colorectal cancers, PIK3CA mutations most commonly occur concomitantly with loss of adenomatous polyposis coli (APC). Here, treatment strategies are investigated that target the PI3K pathway in colon cancers with mutations in APC and PIK3CA Colorectal cancer spheroids with Apc and Pik3ca mutations were generated and characterized ...

2022年4月28日 · Activating mutations in PIK3CA, a driver oncogene that encodes phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit α-isoform (PI3Kα), are among the most common genetic alterations that...

PI3K 相关激酶 (PIKK) 家族成员，包括 DNA-PK，也同样能在 Akt 丝氨酸 473 位点将其磷酸化。 Akt 可被蛋白磷酸酶 2A (PP2A) 以及 PH-结构域富含亮氨酸-重复-包含蛋白磷酸酶 (PHLPP1/2)去磷酸化。 另外，抑癌基因磷酸酶和张力蛋白同源蛋白 (PTEN)，也通过去磷酸化 PIP3 抑制 Akt 活性。 PI3K/Akt 信号通路失调见于多种人类疾病，包括癌症、糖尿病、心血管疾病和神经疾病。 在癌症中，已发现两处可增强 PI3K 内在激酶活性的突变。 另外，人类肿瘤中 PTEN 常发生突变 …