Am J Physiol Cell Physiol AJP: Regulatory, Integrative and Comparative Physiology
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Am J Physiol Cell Physiol 283: C2-C28, 2002; doi:10.1152/ajpcell.00581.2001
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Vol. 283, Issue 1, C2-C28, July 2002

INVITED REVIEW
Cross signaling, cell specificity, and physiology

J. E. Dumont, S. Dremier, I. Pirson, and C. Maenhaut

Institute of Interdisciplinary Research, Free University of Brussels, Campus Erasme, B-1070 Brussels, Belgium

The literature on intracellular signal transduction presents a confusing picture: every regulatory factor appears to be regulated by all signal transduction cascades and to regulate all cell processes. This contrasts with the known exquisite specificity of action of extracellular signals in different cell types in vivo. The confusion of the in vitro literature is shown to arise from several causes: the inevitable artifacts inherent in reductionism, the arguments used to establish causal effect relationships, the use of less than adequate models (cell lines, transfections, acellular systems, etc.), and the implicit assumption that networks of regulations are universal whereas they are in fact cell and stage specific. Cell specificity results from the existence in any cell type of a unique set of proteins and their isoforms at each level of signal transduction cascades, from the space structure of their components, from their combinatorial logic at each level, from the presence of modulators of signal transduction proteins and of modulators of modulators, from the time structure of extracellular signals and of their transduction, and from quantitative differences of expression of similar sets of factors.

signal transduction; effect of hormone modulations; isoforms; combinatorial logic


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