Calmodulin and PI3K Signaling in KRAS Cancers.
Calmodulin and PI3K Signaling in KRAS Cancers.
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DOI：
10.1016/j.trecan.2017.01.007
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发表时间：
2017-03
期刊：
影响因子：
18.4
通讯作者：
Gaponenko V
中科院分区：
文献类型：
--
作者：
Nussinov R;Wang G;Tsai CJ;Jang H;Lu S;Banerjee A;Zhang J;Gaponenko V
钙调素（CaM）独特地促进致癌K-Ras的信号传导;但不是N-Ras或H-Ras。CaM如何与K-Ras相互作用以及如何刺激细胞增殖是KRAS驱动的癌症中最具挑战性的问题之一。早期的数据表明，形成了由K-Ras、PI 3 K α和CaM组成的三元复合物。最近的数据表明磷酸化CaM与PI 3 K α的p85亚基的SH 2结构域结合并激活它，模型表明磷酸化CaM酪氨酸基序与PI 3 K α之间的高亲和力相互作用可以促进致癌K-Ras完全激活PI 3 K α。我们的最新综述讨论了CaM在KRAS驱动的癌症中膜PI 3 K信号传导中的作用。这是重要的，因为它可能有助于开发K-Ras特异性药理学。
Calmodulin (CaM) uniquely promotes signaling of oncogenic K-Ras; but not N-Ras or H-Ras. How CaM interacts with K-Ras and how this stimulates cell proliferation are among the most challenging questions in KRAS-driven cancers. Earlier data pointed to formation of a ternary complex consisting of K-Ras, PI3Kα and CaM. Recent data point to phosphorylated CaM binding to the SH2 domains of the p85 subunit of PI3Kα and activating it. Modeling suggests that the high affinity interaction between the phosphorylated CaM tyrosine motif and PI3Kα, can promote full PI3Kα activation by oncogenic K-Ras. Our up-to-date review discusses CaM’s role in PI3K signaling at the membrane in KRAS-driven cancers. This is significant since it may help development of K-Ras-specific pharmacology.