Inez Lam, Christina M Pickering, Feilim Mac Gabhann
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引用次数: 3
Abstract
Receptor tyrosine kinases (RTKs) are cell membrane proteins that provide cells with the ability to sense proteins in their environments. Many RTKs are essential to development and organ growth. Derangement of RTKs-by mutation or by overexpression-is central to several developmental and adult disorders including cancer, short stature, and vascular pathologies. The mechanism of action of RTKs is complex and is regulated by contextual components, including the existence of multiple competing ligands and receptors in many families, the intracellular location of the RTK, the dynamic and cell-specific coexpression of other RTKs, and the commonality of downstream signaling pathways. This means that both the state of the cell and the microenvironment outside the cell play a role, which makes sense given the pivotal location of RTKs as the nexus linking the extracellular milieu to intracellular signaling and modification of cell behavior. In this review, we describe these different contextual components through the lens of systems biology, in which both computational modeling and experimental "omics" approaches have been used to better understand RTK networks. The complexity of these networks is such that using these systems biology approaches is necessary to get a handle on the mechanisms of pathology and the design of therapeutics targeting RTKs. In particular, we describe in detail three concrete examples (involving ErbB3, VEGFR2, and AXL) that illustrate how systems approaches can reveal key mechanistic and therapeutic insights. This article is categorized under: Biological Mechanisms > Cell Signaling Models of Systems Properties and Processes > Mechanistic Models Translational, Genomic, and Systems Medicine > Therapeutic Methods.
期刊介绍:
Journal Name:Wiley Interdisciplinary Reviews-Systems Biology and Medicine
Focus:
Strong interdisciplinary focus
Serves as an encyclopedic reference for systems biology research
Conceptual Framework:
Systems biology asserts the study of organisms as hierarchical systems or networks
Individual biological components interact in complex ways within these systems
Article Coverage:
Discusses biology, methods, and models
Spans systems from a few molecules to whole species
Topical Coverage:
Developmental Biology
Physiology
Biological Mechanisms
Models of Systems, Properties, and Processes
Laboratory Methods and Technologies
Translational, Genomic, and Systems Medicine