Usage of activating mutations in the analysis of cytokine signal transduction pathways

Cytokine signal transduction pathways are highly redundant and complex. The analysis of the structure and function of signal transduction molecules was conventionally done by using mutated or truncated receptors, dominant negative molecules, and knockout mice. These methods are designed to look at the result of a subtraction of a part of the whole signal transduction pathway. In contrast, analysis using activating mutations of a signal transduction molecule is designed to look at the downstream result of one pathway which originated from the pertinent molecule. This method is less influenced by other signal transduction molecules which may have an overlapping effect on the downstream molecules. By combining both the subtraction and activating methods, we can gain more insight into the complex interactions between signal transduction molecules. An activating mutation of a signal transduction molecule is usually found as an oncogene. However, known oncogenes are not always the molecules of interest. In this review, several methods to create activating mutations of a target molecule are discussed.