The Atypical MAP Kinase ErkB Transmits Distinct Chemotactic Signals through a Core Signaling Module

John M.E. Nichols (Lead / Corresponding author), Peggy Paschke, Sew Peak-Chew, Thomas D. Williams, Luke Tweedy, Mark Skehel, Elaine Stephens, Jonathan R. Chubb, Robert R. Kay

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)
28 Downloads (Pure)

Abstract

Signaling from chemoattractant receptors activates the cytoskeleton of crawling cells for chemotaxis. We show using phosphoproteomics that different chemoattractants cause phosphorylation of the same core set of around 80 proteins in Dictyostelium cells. Strikingly, the majority of these are phosphorylated at an [S/T]PR motif by the atypical MAP kinase ErkB. Unlike most chemotactic responses, ErkB phosphorylations are persistent and do not adapt to sustained stimulation with chemoattractant. ErkB integrates dynamic autophosphorylation with chemotactic signaling through G-protein-coupled receptors. Downstream, our phosphoproteomics data define a broad panel of regulators of chemotaxis. Surprisingly, targets are almost exclusively other signaling proteins, rather than cytoskeletal components, revealing ErkB as a regulator of regulators rather than acting directly on the motility machinery. ErkB null cells migrate slowly and orientate poorly over broad dynamic ranges of chemoattractant. Our data indicate a central role for ErkB and its substrates in directing chemotaxis. Signaling via chemoattractant receptors activates the cytoskeleton to drive chemotaxis. Nichols, Paschke et al. show that in Dictyostelium cells, the atypical MAP kinase ErkB mediates the response to multiple chemoattractants by directly phosphorylating a core set of signaling proteins. Mutants in ErkB and its substrates impair chemotaxis and motility.

Original languageEnglish
Pages (from-to)491-505.e9
Number of pages25
JournalDevelopmental Cell
Volume48
Issue number4
Early online date9 Jan 2019
DOIs
Publication statusPublished - 25 Feb 2019

Keywords

  • chemotaxis
  • Dictyostelium discoideum
  • MAPK signaling
  • phosphoproteomics
  • protein kinase
  • protein phosphorylation
  • signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

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