Disordered Protein Kinase Regions in Regulation of Kinase Domain Cores

Trends Biochem Sci. 2019 Apr;44(4):300-311. doi: 10.1016/j.tibs.2018.12.002. Epub 2019 Jan 2.


Since publication of the crystal structure of protein kinase (PK)A three decades ago, a structural portrait of the conserved kinase core has been drawn. The next challenge is to elucidate structures of full-length kinases and to address the intrinsically disordered regions (IDRs) that typically flank the core as well as the small linear motifs (SLiMs) that are embedded within the IDRs. It is increasingly apparent that unstructured regions integrate the kinase catalytic chassis into multienzyme-based regulatory networks. The extracellular signal-regulated kinase-ribosomal S6 PK-phosphoinositide-dependent kinase (ERK-RSK-PDK) complex is an excellent example to demonstrate how IDRs and SLiMs govern communication between four different kinase catalytic cores to mediate activation and how in molecular terms these promote the formation of kinase heterodimers in a context dependent fashion.

Keywords: cell signaling; disorder; linear motif; protein kinase; protein–protein interaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Intrinsically Disordered Proteins / chemistry*
  • Intrinsically Disordered Proteins / metabolism
  • Models, Molecular
  • Protein Domains
  • Protein Kinases / chemistry*
  • Protein Kinases / metabolism*


  • Intrinsically Disordered Proteins
  • Protein Kinases