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Scavello, Margarethakay, Petlick, AR Alexandra R, Ramesh, Ramya, Thompson, VF Valery F, Lotfi, Pouya, Charest, PG Pascale G, (2017) ' Protein Kinase A regulates the Ras, Rap1, and TORC2 pathways in response to the chemoattractant cAMP in Dictyostelium. ' J. Cell. Sci.
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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 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.
Status: aheadofprint Type: Journal article Source: PUBMED PubMed ID: 28302905
 
Genes addressed in this paper
acaA carA-1 carA-2 piaA pkaC pkaR pkbA pkgB
Topics in this paper
Function/Process



X X

Chemotaxis/Motility
X X
X X

Signal Transduction X X X
X X X X
RNA Levels and Processing X X X X

X X
Genetic Interactions
X X
X


Regulatory Role X X X
X X

Mutants/Phenotypes X X X
X


Regulated By





X X


Genes addressed in this paper
rapA rasC rasG tor
Topics in this paper
Function/Process



Chemotaxis/Motility



Signal Transduction X X X X
RNA Levels and Processing X
X
Genetic Interactions



Regulatory Role



Mutants/Phenotypes



Regulated By X X X X