Evolution, dynamics and dysregulation of kinase signalling

Curr Opin Struct Biol. 2018 Feb:48:133-140. doi: 10.1016/j.sbi.2017.12.008. Epub 2018 Jan 6.

Abstract

Protein kinases are central regulators of most eukaryotic cellular processes. While kinase signalling has been studied for decades, only through recent advances in mass spectrometry have we been able to identify phophosites in large scale and quantify their regulation across conditions. These advances are challenging our understanding of kinase signalling and shedding light into how these systems have evolved. Kinase substrate specificity appears to be strongly conserved but their target phosphosites diverge at a very fast rate. However, less is known about the functional consequences of such changes and the fraction of phosphosites that are crucial for organismal fitness. A better understanding of these evolutionary processes will facilitate the study of disease related genomic alterations that target these signalling circuits.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Catalytic Domain
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / enzymology*
  • Eukaryotic Cells / metabolism
  • Humans
  • Ligands
  • Phosphoproteins / chemistry*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Kinases / chemistry*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Processing, Post-Translational*
  • Signal Transduction*
  • Substrate Specificity

Substances

  • Ligands
  • Phosphoproteins
  • Protein Kinases