Complexity of receptor tyrosine kinase signal processing

Cold Spring Harb Perspect Biol. 2013 Aug 1;5(8):a009043. doi: 10.1101/cshperspect.a009043.

Abstract

Our knowledge of molecular mechanisms of receptor tyrosine kinase (RTK) signaling advances with ever-increasing pace. Yet our understanding of how the spatiotemporal dynamics of RTK signaling control specific cellular outcomes has lagged behind. Systems-centered experimental and computational approaches can help reveal how overlapping networks of signal transducers downstream of RTKs orchestrate specific cell-fate decisions. We discuss how RTK network regulatory structures, which involve the immediate posttranslational and delayed transcriptional controls by multiple feed forward and feedback loops together with pathway cross talk, adapt cells to the combinatorial variety of external cues and conditions. This intricate network circuitry endows cells with emerging capabilities for RTK signal processing and decoding. We illustrate how mathematical modeling facilitates our understanding of RTK network behaviors by unraveling specific systems properties, including bistability, oscillations, excitable responses, and generation of intricate landscapes of signaling activities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Feedback, Physiological / physiology*
  • Gene Expression Regulation, Enzymologic / genetics
  • Gene Expression Regulation, Enzymologic / physiology*
  • Gene Regulatory Networks / genetics*
  • Models, Biological*
  • Receptor Cross-Talk / physiology
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / genetics*
  • Systems Biology

Substances

  • Receptor Protein-Tyrosine Kinases