Nichols, JME;
Paschke, P;
Peak-Chew, S;
Williams, TD;
Tweedy, L;
Skehel, M;
Stephens, E;
... Kay, RR; + view all
(2019)
The Atypical MAP Kinase ErkB Transmits Distinct Chemotactic Signals through a Core Signaling Module.
Developmental Cell
, 48
(4)
491-505.e9.
10.1016/j.devcel.2018.12.001.
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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.
| Type: | Article |
|---|---|
| Title: | The Atypical MAP Kinase ErkB Transmits Distinct Chemotactic Signals through a Core Signaling Module |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.devcel.2018.12.001 |
| Publisher version: | https://doi.org/10.1016/j.devcel.2018.12.001 |
| Language: | English |
| Additional information: | Publishsed © 2018 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/). |
| Keywords: | chemotaxis, signal transduction, MAPK signaling, phosphoproteomics, protein phosphorylation, protein kinase, Dictyostelium discoideum |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10065794 |
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