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

Margarethakay Scavello, Alexandra R. Petlick, Ramya Ramesh, Valery F. Thompson, Pouya Lotfi, Pascale G Charest

Research output: Contribution to journalArticle

7 Scopus citations

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 ACAmediated 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.

Original languageEnglish (US)
Pages (from-to)1545-1558
Number of pages14
JournalJournal of Cell Science
Volume130
Issue number9
DOIs
StatePublished - May 1 2017

Keywords

  • Chemotactic signaling
  • Chemotaxis
  • Directional sensing
  • Migration
  • Negative feedback
  • PKA

ASJC Scopus subject areas

  • Cell Biology

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