Open AccessRole of G-proteins and S/T phosphorylation sites in the transition of Activator of G-Protein signaling 3 to cell puncta
Author(s) -
Ali Vural,
Ersin Fadıllıoğlu,
Fatih Mehmet Keleşoğlu,
Dzwokai Ma,
Stephen M. Lanier
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.216507
Subject(s) - biology , phosphorylation , activator (genetics) , microbiology and biotechnology , signal transduction , transition (genetics) , signaling proteins , biochemistry , gene
Activator of G-protein Signaling 3 (AGS3) exhibits broad functional diversity and oscillates among different subcellular compartments in a regulated manner. AGS3 consists of a tetratricopeptide repeat (TPR) domain and a G-protein regulatory (GPR) domain. We tested the hypothesis that phosphorylation of the AGS3 GPR domain regulated its subcellular distribution and functionality. In contrast to the cortical and/or diffuse non-homogeneous distribution of WT AGS3. AGS3 lacking 24 S/T phosphorylation sites in the GPR domain localized to cytosolic puncta and this was dependent upon a single amino acid (T602). The punctate distribution of AGS3-T602A was rescued by co-expression of Gαi/o. but not Gαs or Gαq. AGS3-T602A or WT AGS3 following treatment with alkaline phosphatase both exhibited a gel shift by SDS-PAGE as compared to untreated WT AGS3. The punctate distribution of AGS3-T602A was lost with the conversion construct AGS3-A602T*, but was still present upon T602 substitution with glutamate or aspartate. These data implicate dynamic phosphorylation as a discrete mechanism to regulate the subcellular distribution of AGS3 and associated functionality.