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Dev Cell. 2018 Dec 31. pii: S1534-5807(18)31034-7. doi: 10.1016/j.devcel.2018.12.001. [Epub ahead of print]

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

Author information

1
Cell Biology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; MRC Laboratory for Molecular Cell Biology, University College London, Gower St., London WC1E 6BT, UK. Electronic address: j.nichols@ucl.ac.uk.
2
Cell Biology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cancer Research UK (CRUK) Beatson Institute, University of Glasgow, Bearsden, Glasgow G61 1BD, UK. Electronic address: ppaschke@mrc-lmb.cam.ac.uk.
3
Cell Biology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
4
Cancer Research UK (CRUK) Beatson Institute, University of Glasgow, Bearsden, Glasgow G61 1BD, UK.
5
Cell Biology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Pfizer Inc, 1 Burtt Road, Andover, MA 01810, USA.
6
MRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, Gower St., London WC1E 6BT, UK.
7
Cell Biology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: rrk@mrc-lmb.cam.ac.uk.

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.

KEYWORDS:

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

PMID:
30612939
DOI:
10.1016/j.devcel.2018.12.001
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