MAPKs in development: insights from Dictyostelium signaling pathways

Hadwiger, Jeffrey A.; Nguyen, Hoa D.

doi:10.1515/bmc.2011.004

Cited by 18 publications

(19 citation statements)

References 73 publications

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“…Extracellular signal–regulated kinases (ERKs) are a conserved group of mitogen-activated kinases (MAPKs; Cargnello and Roux, 2011). Dictyostelium has two MAPKs, ERK1 and ERK2 (Hadwiger and Nguyen, 2011). In starved cells, cAMP causes a rapid increase in ERK2 phosphorylation, which is followed by an increase in ERK1 phosphorylation, and the ERK1 phosphorylation can be detected by an anti-phospho MAPK antibody that detects threonine phosphorylation at a conserved TXY motif (Schwebs and Hadwiger, 2015).…”

Section: Resultsmentioning

confidence: 99%

An endogenous chemorepellent directs cell movement by inhibiting pseudopods at one side of cells

Rijal

Consalvo

Lindsey

et al. 2019

MBoC

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Eukaryotic chemoattraction signal transduction pathways, such as those used by Dictyostelium discoideum to move toward cAMP, use a G protein–coupled receptor to activate multiple conserved pathways such as PI3 kinase/Akt/PKB to induce actin polymerization and pseudopod formation at the front of a cell, and PTEN to localize myosin II to the rear of a cell. Relatively little is known about chemorepulsion. We previously found that AprA is a chemorepellent protein secreted by Dictyostelium cells. Here we used 29 cell lines with disruptions of cAMP and/or AprA signal transduction pathway components, and delineated the AprA chemorepulsion pathway. We find that AprA uses a subset of chemoattraction signal transduction pathways including Ras, protein kinase A, target of rapamycin (TOR), phospholipase A, and ERK1, but does not require the PI3 kinase/Akt/PKB and guanylyl cyclase pathways to induce chemorepulsion. Possibly as a result of not using the PI3 kinase/Akt/PKB pathway and guanylyl cyclases, AprA does not induce actin polymerization or increase the pseudopod formation rate, but rather appears to inhibit pseudopod formation at the side of cells closest to the source of AprA.

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Section: Resultsmentioning

confidence: 99%

An endogenous chemorepellent directs cell movement by inhibiting pseudopods at one side of cells

Rijal

Consalvo

Lindsey

et al. 2019

MBoC

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“…Cells lacking both Akt homologs PkbA and PkgB, RasC or PakD have abolished aggregation in response to polyphosphate and starvation (Meili et al, 2000;Lim et al, 2001;Garcia et al, 2014), while cells lacking PkbA or NapA show delayed aggregation upon starvation but do not respond to polyphosphate-induced aggregation (Meili et al, 1999;Ibarra et al, 2006). Cells lacking Erk1 undergo starvation-induced aggregation, but form smaller aggregates than do wild-type cells and become stalled at later stages of development (Hadwiger and Nguyen, 2011), yet are unresponsive to polyphosphate-induced aggregation. These results suggest that some pathway components of polyphosphate and starvation-induced aggregation are shared, while polyphosphate also utilizes unique components.…”

Section: Proteasome Inhibition Alone Is Not Sufficient To Induce Devementioning

confidence: 99%

Extracellular polyphosphate signals through Ras and Akt to prime Dictyostelium discoideum cells for development

Suess

Watson

Chen

et al. 2017

Journal of Cell Science

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Linear chains of five to hundreds of phosphates called polyphosphate are found in organisms ranging from bacteria to humans, but their function is poorly understood. In Dictyostelium discoideum, polyphosphate is used as a secreted signal that inhibits cytokinesis in an autocrine negative feedback loop. To elucidate how cells respond to this unusual signal, we undertook a proteomic analysis of cells treated with physiological levels of polyphosphate and observed that polyphosphate causes cells to decrease levels of actin cytoskeleton proteins, possibly explaining how polyphosphate inhibits cytokinesis. Polyphosphate also causes proteasome protein levels to decrease, and in both Dictyostelium and human leukemia cells, decreases proteasome activity and cell proliferation. Polyphosphate also induces Dictyostelium cells to begin development by increasing expression of the cell-cell adhesion molecule CsA (also known as CsaA) and causing aggregation, and this effect, as well as the inhibition of proteasome activity, is mediated by Ras and Akt proteins. Surprisingly, Ras and Akt do not affect the ability of polyphosphate to inhibit proliferation, suggesting that a branching pathway mediates the effects of polyphosphate, with one branch affecting proliferation, and the other branch affecting development.

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“…The soil amoebae Dictyostelium discoideum has only two MAPKs, ERK1 and ERK2 (39% primary sequence identity), and both play important roles in the developmental life cycle that allows solitary cells to aggregate and develop into a fruiting body structure consisting of a stalk and a mass of spores [3]. During this multicellular development, intercellular signaling mediated through G protein coupled receptors regulates the differentiation and sorting of prespore and prestalk cells within the aggregate and some of these signaling pathways involve MAPK activity.…”

Section: Introductionmentioning

confidence: 99%

The Dictyostelium MAPK ERK1 is phosphorylated in a secondary response to early developmental signaling

Schwebs¹,

Hadwiger²

2015

Cellular Signalling

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Previous reports have suggested that the two mitogen-activated protein kinases (MAPKs) in Dictyostelium discoideum, ERK1 and ERK2, can be directly activated in response to external cAMP even though these MAPKs play different roles in the developmental life cycle. To better characterize MAPK regulation, the levels of phosphorylated MAPKs were analyzed in response to external signals. Only ERK2 was rapidly phosphorylated in response to the chemoattractants, cAMP and folate. In contrast, the phosphorylation of ERK1 occurred as a secondary or indirect response to these stimuli and this phosphorylation was enhanced by cell-cell interactions, suggesting that other external signals can activate ERK1. The phosphorylation of ERK1 or ERK2 did not require the function of the other MAPK in these responses. Folate stimulation of a chimeric population of erk1− and gα4− cells revealed that the phosphorylation of ERK1 could be mediated through an intercellular signal other than folate. Loss of ERK1 function suppressed the developmental delay and the deficiency in anterior cell localization associated with gα5− mutants suggesting that ERK1 function can be down regulated through Gα5 subunit-mediated signaling. However, no major changes in the phosphorylation of ERK1 were observed in gα5− cells suggesting that the Gα5 subunit signaling pathway does not regulate the phosphorylation of ERK1. These findings suggest that the activation of ERK1 occurs as a secondary response to chemoattractants and that other cell-cell signaling mechanisms contribute to this activation. Gα5 subunit signaling can down regulate ERK1 function to promote prestalk cell development but not through major changes to the level of phosphorylated ERK1.

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MAPKs in development: insights from Dictyostelium signaling pathways

Cited by 18 publications

References 73 publications

An endogenous chemorepellent directs cell movement by inhibiting pseudopods at one side of cells

An endogenous chemorepellent directs cell movement by inhibiting pseudopods at one side of cells

Extracellular polyphosphate signals through Ras and Akt to prime Dictyostelium discoideum cells for development

The Dictyostelium MAPK ERK1 is phosphorylated in a secondary response to early developmental signaling

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