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Related data published while this paper was in production

Posted by PGruppuso on 18 Jul 2011 at 19:40 GMT

Rapamycin-regulated Phosphorylation Events
http://plosone.org/article/info:doi/10.1371/journal.pone.0021729#article1.body1.sec3.sec3.p1

While the present manuscript was in production, two papers appeared in Science, one by Hsu et al. ( Science 332:1317-1322, 2011) and the other by Yu et al. (Science 332: 1322-1326, 2011), identified a number of new downstream targets of mTOR. These investigators, using cell lines, employed phosphoproteomic strategies similar to those employed in the present manuscript. Among the phosphosites they identified are several that are contained in our list of rapamycin-responsive candidate phosphorylation sites in liver that had not been previously characterized (Table 1). These include hepatoma-derived growth factor 3 (HDGFRP2) Ser450, identified as mTOR-regulated by both groups. In addition, eukaryotic initiation factor 3a (EIF3A) Ser584 and autophagy-related protein 2 homolog A (ATG2A) Ser1246 sites were identified as down-regulated in response to rapamycin by Yu et al. We identified the same EIF3A Ser584 site and the nearby ATG2A Ser1243 as rapamycin-responsive. Carbomyl-phosphate synthase 2 (CAD) Ser1859 site was identified by Hsu et al. as affected by rapamycin and torin. Finally, both research groups identified growth factor receptor-bound protein 10 (GRB10) as an mTOR substrate involved in regulating PI3K activity through feedback inhibition. We did not identify GRB10 in our studies. This was expected because we have previously shown that GRB10 is not expressed in adult liver (Gruppuso et al. Biochim Biophys Acta 1494: 242-247, 2000). However, we did identify phosphorylation of GRB7 at Ser364 as rapamycin-responsive. We hypothesize that this phosphosite is functionally analogous to the mTOR-regulated phosphosite on GRB10.

No competing interests declared.