Somatic Cell Genetic Dissection of Interferon Signal Transduction Pathways

Abstract

Over the last half decade, the interferon α/β and interferon γ signaling systems have been the topic of a most elegant series of experiments. While classical biochemistry has revealed much about each of the protagonists in these pathways, their involvement and the order in which they become involved has only recently come to light from the investigation of a series of cellular mutants in the IFNα/β and IFNγ signaling pathways (reviewed in ref. 221). In this chapter we focus upon the use of somatic cell genetics as a tool with which to uncover the molecules involved in connecting the cell surface receptors for interferon α/β and interferon γ with the genes induced by these cytokines. The signaling framework which emerged from these studies has proved to be a general feature of all signaling downstream of cytokine receptors, and provided the mechanistic underpinning for the JAK-STAT pathway. The first piece in the puzzle was the generation of cell lines defective in IFNα/β signaling.