Quantitative modeling perspectives on the ErbB system of cell regulatory processes.

TitleQuantitative modeling perspectives on the ErbB system of cell regulatory processes.
Publication TypeJournal Article
Year of Publication2009
AuthorsLazzara, MJ, Lauffenburger, DA
JournalExp Cell Res
Volume315
Issue4
Pagination717-25
Date Published2009 Feb 15
ISSN1090-2422
KeywordsAnimals, Autocrine Communication, Dimerization, Humans, Models, Biological, Paracrine Communication, Protein Binding, Protein Transport, Receptor, erbB-2
Abstract

The complexities of the processes involved in ErbB-mediated regulation of cellular phenotype are broadly appreciated, so much so that it might be reasonably argued that this highly studied system provided significant impetus for the systems perspective on cell signaling processes in general. Recent years have seen major advances in the level of characterization of the ErbB system as well as our ability to make measurements of the system. This new data provides significant new insight, while at the same time creating new challenges for making quantitative statements and predictions with certainty. Here, we discuss recent advances in each of these directions and the interplay between them, with a particular focus on quantitative modeling approaches to interpret data and provide predictive power. Our discussion follows the sequential order of ErbB pathway activation, beginning with considerations of receptor/ligand interactions and dynamics, proceeding to the generation of intracellular signals, and ending with determination of cellular phenotype. As discussed herein, these processes become increasingly difficult to describe or interpret in terms of traditional models, and we review emerging methodologies to address this complexity.

DOI10.1016/j.yexcr.2008.10.033
Alternate JournalExp. Cell Res.
PubMed ID19022246
Grant ListR01-CA096504 / CA / NCI NIH HHS / United States
U54-CA112967 / CA / NCI NIH HHS / United States