How Do Protein Kinases Take a Selfie (Autophosphorylate)?

Jonah Beenstock, Navit Mooshayef, David Engelberg*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations

Abstract

Eukaryotic protein kinases (EPKs) control most biological processes and play central roles in many human diseases. To become catalytically active, EPKs undergo conversion from an inactive to an active conformation, an event that depends upon phosphorylation of their activation loop. Intriguingly, EPKs can use their own catalytic activity to achieve this critical phosphorylation. In other words, paradoxically, EPKs catalyze autophosphorylation when supposedly in their inactive state. This indicates the existence of another important conformation that specifically permits autophosphorylation at the activation loop, which in turn imposes adoption of the active conformation. This can be considered a prone-to-autophosphorylate conformation. Recent findings suggest that in prone-to-autophosphorylate conformations catalytic motifs are aligned allosterically, by dimerization or by regulators, and support autophosphorylation in cis or trans.

Original languageAmerican English
Pages (from-to)938-953
Number of pages16
JournalTrends in Biochemical Sciences
Volume41
Issue number11
DOIs
StatePublished - 1 Nov 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

  • allostery
  • autophosphorylation
  • dimerization
  • protein kinase.

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