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    Protein kinase A regulates the Ras, Rap1 and TORC2 pathways in response to the chemoattractant cAMP in Dictyostelium

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    Author
    Scavello, Margarethakay
    Petlick, Alexandra R. cc
    Ramesh, Ramya
    Thompson, Valery F.
    Lotfi, Pouya
    Charest, Pascale G. cc
    Affiliation
    Univ Arizona, Dept Chem & Biochem
    Issue Date
    2017-05-01
    Keywords
    Chemotaxis
    Migration
    PKA
    Negative feedback
    Directional sensing
    Chemotactic signaling
    
    Metadata
    Show full item record
    Publisher
    COMPANY OF BIOLOGISTS LTD
    Citation
    Protein 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
    Journal
    Journal of Cell Science
    Rights
    © 2017. Published by The Company of Biologists Ltd
    Collection Information
    This 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 repository@u.library.arizona.edu.
    Abstract
    Efficient 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.
    Note
    12 month embargo; Published online May 1, 2017.
    ISSN
    0021-9533
    1477-9137
    PubMed ID
    28302905
    DOI
    10.1242/jcs.177170
    Version
    Final published version
    Sponsors
    National Institutes of Health [GM008804]; U.S. Public Health Service [GM037830]; American Cancer Society [127940-RSG-15-024-01-CSM]
    Additional Links
    http://jcs.biologists.org/lookup/doi/10.1242/jcs.177170
    ae974a485f413a2113503eed53cd6c53
    10.1242/jcs.177170
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