Protein kinase A regulates the Ras, Rap1 and TORC2 pathways in response to the chemoattractant cAMP in Dictyostelium
Author
Scavello, MargarethakayPetlick, Alexandra R.

Ramesh, Ramya
Thompson, Valery F.
Lotfi, Pouya
Charest, Pascale G.

Affiliation
Univ Arizona, Dept Chem & BiochemIssue Date
2017-05-01
Metadata
Show full item recordPublisher
COMPANY OF BIOLOGISTS LTDCitation
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 ScienceJournal
Journal of Cell ScienceRights
© 2017. Published by The Company of Biologists LtdCollection 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
0021-95331477-9137
PubMed ID
28302905Version
Final published versionSponsors
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.177170ae974a485f413a2113503eed53cd6c53
10.1242/jcs.177170