Calmodulin (CaM) uniquely promotes signaling by oncogenic K-Ras, but not by 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 the formation of a ternary complex consisting of K-Ras, phosphatidylinositide-3-kinase α (PI3Kα), and CaM. Recent data indicate that phosphorylated CaM binds to the Src homology 2 (SH2) domains of the p85 subunit of PI3Kα and activates 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. This review discusses the role of CaM in PI3K signaling at the membrane in KRAS-driven cancers. This is significant because it may help the development of K-Ras-specific pharmacology.

钙调蛋白（CaM）独特地通过致癌的K-Ras促进信号传导，而不是通过N-Ras或H-Ras促进信号传导。CaM如何与K-Ras相互作用以及如何刺激K-Ras是KRAS驱动的癌症中最具挑战性的问题。较早的数据表明形成了由K-Ras，磷脂酰肌醇-3-激酶α（PI3Kα）和CaM组成的三元复合物。最近的数据表明，磷酸化的CaM与PI3Kαp85亚基的Src同源2（SH2）域结合并激活它。建模表明，磷酸化CaM酪氨酸基序与PI3Kα之间的高亲和力相互作用可以促进致癌K-Ras完全激活PI3Kα。这篇综述讨论了CaM在KRAS膜的PI3K信号传导中的作用。驱动的癌症。这很重要，因为它可以帮助开发K-Ras特异性药理学。