Hopscotch/Tumorous Lethal: A JAK Family Member from Drosophila Melanogaster
Historically, organisms such as the fruit fly (Drosophila melanogaster or D. melanogaster) and the nematode worm (Caenorhabditis elegans or C. elegans), for which sophisticated genetic approaches have been developed, have proven to be immensely useful tools for the investigation of signal transduction pathways. The degree of identity which underlies the intracellular signal transduction pathways of organisms as diverse as C. elegans and the laboratory mouse (Mus musculus) is reassuring, and suggests that the information which has emerged from the study of lower metazoans is tremendously pertinent to our notions of how signal transduction works in human cells. In choosing to explore a signal transduction pathway such as the JAK-STAT pathway in mammalian cells, the limitations of the experimental systems available must be acknowledged. Thus, despite the remarkable advances in our understanding of this pathway which have emerged from the study of cellular mutants of interferon-dependent signaling, coupled with the intense focus on the biochemistry of this pathway in a host of cytokine-dependent signaling pathways, there remain limitations to each of these approaches which will confound a fuller understanding of how the JAK-STAT pathway fits into the network of signal transduction within any given cell. For example, investigation of the interferon-dependent signaling mutants described in chapter 6, will only facilitate an examination of the JAK-STAT pathway in the context of the activation of the particular promoter used in the selection protocol under which the cells were originally generated. In contrast, the use of the coordinated embryonic development of an entire organism as an “assay” for molecules which might interact with components of the JAK-STAT pathway(s) is likely to present a more realistic picture of how it is integrated into the intracellular signaling network of many thousands of developmentally different cells and cell types. Thus, while such an assay system is more difficult to establish, the dividends of success would be considerably greater.
KeywordsTyrosine Glycine Encapsulation Lost Diphosphate
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