|Page Contents: Abstract|
Nichols, JME John M E, Paschke, Peggy, Peak-Chew, Sew, Williams, TD Thomas D, Tweedy, Luke, Skehel, Mark, Stephens, Elaine, Chubb, JR Jonathan R, Kay, RR Robert R, (2018)
' The Atypical MAP Kinase ErkB Transmits Distinct Chemotactic Signals through a Core Signaling Module. '
|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.|
|Status:||aheadofprint||Type:||Journal article||Source:||PUBMED||PubMed ID:||30612939|