Protein kinase A regulates the Ras, Rap1 and TORC2 pathways in response to the chemoattractant cAMP in Dictyostelium
Petlick, Alexandra R.
Thompson, Valery F.
Charest, Pascale G.
AffiliationUniv Arizona, Dept Chem & Biochem
MetadataShow full item record
PublisherCOMPANY OF BIOLOGISTS LTD
CitationProtein kinase A regulates the Ras, Rap1 and TORC2 pathways in response to the chemoattractant cAMP in Dictyostelium 2017, 130 (9):1545 Journal of Cell Science
JournalJournal of Cell Science
Rights© 2017. Published by The Company of Biologists Ltd
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractEfficient directed migration requires tight regulation of chemoattractant signal transduction pathways in both space and time, but the mechanisms involved in such regulation are not well understood. Here, we investigated the role of protein kinase A (PKA) in controlling signaling of the chemoattractant cAMP in Dictyostelium discoideum. We found that cells lacking PKA display severe chemotaxis defects, including impaired directional sensing. Although PKA is an important regulator of developmental gene expression, including the cAMP receptor cAR1, our studies using exogenously expressed cAR1 in cells lacking PKA, cells lacking adenylyl cyclase A (ACA) and cells treated with the PKA-selective pharmacological inhibitor H89, suggest that PKA controls chemoattractant signal transduction, in part, through the regulation of RasG, Rap1 and TORC2. As these pathways control the ACA-mediated production of intracellular cAMP, they lie upstream of PKA in this chemoattractant signaling network. Consequently, we propose that the PKA-mediated regulation of the upstream RasG, Rap1 and TORC2 signaling pathways is part of a negative feedback mechanism controlling chemoattractant signal transduction during Dictyostelium chemotaxis.
Note12 month embargo; Published online May 1, 2017.
VersionFinal published version
SponsorsNational Institutes of Health [GM008804]; U.S. Public Health Service [GM037830]; American Cancer Society [127940-RSG-15-024-01-CSM]
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