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Cell, Vol. 85, 13–14, April 5, 1996, Copyright 1996 by Cell Press Book Review

His–Asp Phosphorelay: Two Components or More?

Two-Component Signal Transduction. Edited By James A. Hoch and Thomas J. Silhavy Washington, DC: ASM Press. (1995). 504 pp. $79.00. to avoid further confusion. While numerical designations refer to the first and second component respectively, Bacteria are constantly bombarded by rapidly changing alphabetical designations originate from the response environmental stresses (nutrition, toxic chemicals, os- regulator being the first transcript preceeding the sensor molarity, oxidative stress, etc.), and adaptation is essen- protein when sharing an operon (e.g., NRIϭNtrC while tial for survival. For these adaptive processes, the major NRIIϭNtrB!). In addition to the His-Asp phosphorelay players are the sensor-kinase (usually a transmembrane system, there are two other classes of bacterial protein receptor) and the response regulator which mediates kinases (metabolite-activated protein kinases, and pho- changes in gene expression or locomotion. The sensor- sphoenol pyruvate-dependent phosphotransferase sys- kinase utilizes ATP to phosphorylate a histidine residue. tems), and this is not apparent to the reader. Clear defini- Subsequently, the phosphoryl group is transferred to tions of kinase, phosphotransferase, and phosphatase an aspartyl residue on the response regulator which enzymatic activities would also aid the reader in discern- causes a functional switch in the response regulator. ing which proteins confer which activities. Unfortu- The uniqueness of this system is that signal transduction nately, the brief historical perspective offered at the out- is carried out by the reversible phosphorelay of a high set of this book does not properly guide the uninitiated. energy phosphate between histidine and aspartate resi- General principles are described in Section I of this book. Parkinson et al. provide an informative description dues. This is distinctively different from signal transduc- of basic techniques useful for a novice in this field. While tion using serine, threonine, or tyrosine residues, in this chapter could have been strengthened by the in- which the flow of the phosphoryl group is irreversible. clusion of his own recent data, Parkinson’s simplistic Publication of this book is timely because so-called two- overview of the system is valuable. The chapter on struc- component signal transducing systems, once believed ture-function relationships and catalytic mechanisms to widely prevail only in prokaryotes, have recently been authored by Stock et al. provides a comprehensive and identified in eukaryotes (reviewed by Ruis and Schuller, insightful review which also highlights the major differ- 1995, Bioessays 17, 959–965). The book of 488 pages ences between serine/threonine kinases and histidine was edited by two leaders in the field. Consisting of 29 kinases. chapters, it certainly would have been a heroic task for Models of “two-component” systems are offered in the editors to have each contributor write a comprehen- Section II.Systems covered include: nitrogen regulation, sive review on each topic. Some chapters are indeed chemotaxis, porin regulation, and sporulation. Strengths successful as they are extremely well written and very in this section include the chapter on sporulation au- informative. On the other hand, many chapters seem to thored by Hoch which is very well written and includes be an abbreviated summary of a specific topic and are many unpublished results. Response regulator func- not as thought provoking. tions for these same systems are further described in While the naming of so-called two-component sys- Section III, which would better serve the reader if these tems has been well accepted, it is often misleading. chapters were incorporated into chapters covering simi- Histidyl-aspartyl signal transduction systems may have lar systems in Section II. originated as a simple sensor-kinase and response reg- The remaining sections of the book are mainly of inter- ulator pathway, but the system has certainly evolved est to experienced signal transduction researchers: into a multi-component pathway in many systems. At Section IV Cellular Physiology, Section V Pathogenesis, least seven components are involved in chemotaxis, and Section VI Cellular Communication and Develop- where the histidine kinase is downstream of the chemo- ment provide available details for many of the less well receptor sensor; unique separate phosphatases exist in known “two-component” systems. Many of these sys- nitrogen regulation and sporulation; and a multi-step tems are still emerging and contain putative sites of phosphorelay (His Asp His Asp) is used in sporula- phosphorylation and activation domains. → → → tion. The His-Asp phosphorelay can also reside within Overall, the book is useful for graduate students and a single protein (e.g., ArcB and BvgS). This confusion researchers who are probing signal transduction path- further extends to the virulence regulatory system in ways in prokaryotic as well as eukaryotic systems. If Vibrio cholerae, which is described as a three-compo- some chapters are selectively chosen, newcomers can nent system. Perhaps a more appropriate name for this benefit as well. If I were asked to choose three chapters evolving system would be the His-Asp phosphorelay to read, I would enthusiastically recommend Stock et system. al., Ninfa et al., and Hoch. It is disappointing, however, In addition to updating the name for this system, re- that there is neither section nor chapter dedicated to the searchers in this field need to agree on nomenclature structures of the receptor domains or transmembrane Cell 14

domains of chemotactic receptors. It should also be Holbrook, N. J., Martin, G. R., Lockshin, R. A. (1996). Cellular Aging noted that undue emphasis is placed on the phospho- and Cell Death. Wiley Publishers, New York. 319 pp. $89.95. transferase activity of the response regulator, while reg- Karn, J. (1996). HIV Volume 1 Virology and Immunology. Oxford ulation of the histidine kinase is often neglected. The University Press, New York. 275 pp. $79.00. importance of the regulation of the phosphatase is also Karn, J. (1996). HIV Volume 2 Biochemistry, Molecular Biology, and underplayed. It may have been useful to include a glos- Drug Discovery. Oxford University Press, New York. 327 pp. $79.00. sary of terms for clarification. The last note pertains to the front cover, in which the artist could have improved Karp, G. (1996). Cell and Molecular Biology: Concepts and Experi- ments. John Wiley & Sons, New York. 773 pp. $72.95. the depiction of the His-Asp phosphorelay system as well as fixing the wrongly turned DNA helix! Neverthe- Leach, D. R. (1996). Genetic Recombination. Blackwell Science, less, this ambitious book represents existing His-Asp Cambridge, Massachusetts. 192 pp. $34.95. phosphorelay systems and succeeds in its attempt to Markie, D. (1996). Yeast Artificial Chromosome Protocols. Humana document the current state of research while high- Press, Totowa, New Jersey. 378 pp. $69.50. lighting the numerous questions which remain unan- National Research Council. (1996). National Science Education swered. Standards. Natl. Academy Press, Washington, DC. 262 pp. $16.50. I asked a postdoctoral fellow, Zheng Huang, who just Sell, S. (1996). Immunology, Immunopathology & Immunity. Apple- began working on osmoregulation in my lab as well as ton & Lange, Stamford, Connecticut. 1014 pp. $65.00. three senior graduate students, Heiyoung Park, Rinku Sobral, B. W. (1996). The Impact of Plant Molecular Genetics. Birk- Dutta, and Linda Egger, who have been working for hauser, Boston, Massachusetts. 348 pp. $89.50. quite some time on the system to also review this book. Trower, M. K. (1996). In Vitro Mutagenesis Protocols. Humana Press, Additional chapters in the latter sections of the book Totowa, New Jersey. 390 pp. $69.50. that should also be highly recommended include: 13, 14, Webb, C., Dervakos, G. A. (1996). Studies in Viable Cell Immobiliza- 17, 20, 21, 23, and 29. While covering complexpathways, tion. Academic Press, San Diego, California. 198 pp. $69.96. these chapters were exceptionally well written and Wexler, A. (1995). Mapping Fate. Times Books, Random House, clearly presented. Overall, this book provides a good Inc., New York. 294 pp. $23.00. overview of the His-Asp phosphorelay system and will serve as a valuable reference for future research.

Masayori Inouye Department of Biochemistry Robert Wood Johnson Medical School Piscataway, New Jersey 08854

Books Received Ashley, R. H. (1996). Ion Channels: A Practical Approach. Oxford University Press, New York. 302 pp. $49.00. Briscoe, M. H. (1996). Preparing Scientific Illustrations: A Guide to Better Posters, Presentations, and Publications. Springer-Verlag, New York. 204 pp. $29.95. Ca´ rdenaz, M. L. (1995). Glucokinase: Its Regulation and Its Role in Liver Metabolism. R. G. Landes, Georgetown, Texas. 206 pp. $89.00. Clapp, J. P. (1996). Species Diagnostics Protocols: PCR and Other Nucleic Acid Methods. Humana Press, Totowa, New Jersey. 416 pp. $69.50. Coligan, J. E., Dunn, B. M., Ploegh, H. L., Speicher, D. W., and Wingfield, P. T. (1995). Current Protocols in Protein Science. John Wiley & Sons, New York. pp. $340.00. Cortese, R. (1996). Combinatorial Libraries: Synthesis, Screening and Application Potential. Walter de Gruyter, Berlin, Germany. 232 pp. $90.00. Dugas, H. (1996). Bioorganic Chemistry: A Chemical Approach to Enzyme Action. Springer-Verlag, New York. 700 pp. $49.95. Evans, I. H. (1996). Yeast Protocols Methods in Cell and Molecular Biology. Humana Press, Totowa, New Jersey. 433 pp. $74.50. Fan, A. M., Chang, L. W. (1996). Toxicology and Risk Assessment: Principles; Methods; and Applications. Marcel Dekker, New York. 859 pp. $195.00. Fink, R. (1995). CELLebration. Sinauer Associates, Sunderland, MA. pp. $85.00. Hames, B. D., Higgins, S. J. (1996). Gene Probes 2. Oxford University Press, New York. 419 pp. $57.00. Harwood, A. J. (1996). Basic DNA and RNA Protocols. Humana Press, Totowa, New Jersey. 514 pp. $69.50.