Cell Signaling Tomorrow

As the humane genome and importantly the genomes of several other key research paradigms reach completion in terms of sequence, interpretation, and full annotation, it will be possible to know, in a general sense, the complete complement of proteins, involved in cell signaling. Of course, this "signaling proteome" will contain a vast number of variants arising from message splicing and posttranslational modification. Appreciating how all of these variants interact as a function of time in response to stimulation will be a mammoth if not an infinite task. But, this level of knowledge will not be required to make considerable advances over what we know at present. Indeed, we can expect that "expression proteomics," which some really define as

"systems biology," will provide much insight in the coming years, particularly through the clever applications of advances in separations methodology, mass spectrometry, and hybridization assays. Both protein and nucleic acid arrays have already demonstrated their worth, and much more information will be obtained from these powerful techniques. Of utmost importance will be the application of quantification to all types of measurements so that these data can eventually be accurately modeled to produce a true picture of signal fluxes through cells as they undergo their tran-scriptional, phenotypic, and ultimately cell and organ responses. Although one cannot accurately predict over the next ten years what discoveries will be made, other than that there will be many and some of them will be quite unexpected, it seems certain that cell signaling will remain one of the primary areas of expanding biological research. It also seems safe to predict that many singularly important findings in terms of human and animal health will be made and that society, at all levels, will be the better for these efforts.

References

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2. Wright, R. D. (1978). The origin of the term "hormone." Trends in Biochem. Sci. 3, 275.

3. Schaefer, E. A. (1916). The Endocrine Organs. London, 6.

4. Banting, F. G. and Best, C. H. (1922). The internal secretion of the pancreas. J. Lab. Clin. Med. 7, 251-266.

5. Levi-Montalcini, R. (1975). NGF: an unchartered route, in Wooden, F. G., Swazey, J. P. and Adelman, G., Eds., Neurosciences: Paths of Discovery, pp. 243-265. MIT, Cambridge, MA.

6. Cowan, W. M. (2001). Viktor Hamburger and Rita Levi-Montalcini: the path to the discovery of nerve growth factor. Annu. Rev. Neuroscie. 24, 551-600.

7. Hamburger, V. (1989). The journey of a neuroembryologist. Annu. Rev. Neurosci. 12, 1-12.

8. Levi-Montalcini, R. (1987). The nerve growth factor 35 years later. Science 237, 1154-1162.

9. Angeletti, R. H. and Bradshaw, R. A. (1971). Nerve growth factor from mouse submaxillary gland: amino acid sequence. Proc. Natl. Acad. Sci. USA 68, 2417-2420.

10. Savage, C. R., Inagami, T., and Cohen, S. (1972). The primary structure of epidermal growth factor. J. Biol. Chem. 247, 7612-7621.

11. Frazier, W. A., Angeletti, R. H., and Bradshaw, R. A. (1972). Nerve growth factor and insulin. Science 176, 482-488.

12. Raffioni, S., Buxser, S. E., and Bradshaw, R. A. (1993). The receptors for nerve growth factor and other neurotrophins. Annu. Rev. Biochem. 62, 823-850.

13. Robison, G. A., Butcher, R. W., and Sutherland, E. W. (1971). Cyclic AMP. Academic Press, San Diego.

14. Ushiro, H. and Cohen, S. (1980). Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J. Biol. Chem. 255, 8363-8365.

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Part I

Initiation: Extracellular and Membrane Events

James A. Wells, Editor

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Part I

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