| First Author | Bartley CM | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 5 | Pages | e96956 |
| PubMed ID | 24806451 | Mgi Jnum | J:217364 |
| Mgi Id | MGI:5613795 | Doi | 10.1371/journal.pone.0096956 |
| Citation | Bartley CM, et al. (2014) FMRP S499 is phosphorylated independent of mTORC1-S6K1 activity. PLoS One 9(5):e96956 |
| abstractText | Hyperactive mammalian target of rapamycin (mTOR) is associated with cognitive deficits in several neurological disorders including tuberous sclerosis complex (TSC). The phosphorylation of the mRNA-binding protein FMRP reportedly depends on mTOR complex 1 (mTORC1) activity via p70 S6 kinase 1 (S6K1). Because this phosphorylation is thought to regulate the translation of messages important for synaptic plasticity, we explored whether FMRP phosphorylation of the S6K1-dependent residue (S499) is altered in TSC and states of dysregulated TSC-mTORC1 signaling. Surprisingly, we found that FMRP S499 phosphorylation was unchanged in heterozygous and conditional Tsc1 knockout mice despite significantly elevated mTORC1-S6K1 activity. Neither up- nor down-regulation of the mTORC1-S6K1 axis in vivo or in vitro had any effect on phospho-FMRP S499 levels. In addition, FMRP S499 phosphorylation was unaltered in S6K1-knockout mice. Collectively, these data strongly suggest that FMRP S499 phosphorylation is independent of mTORC1-S6K1 activity and is not altered in TSC. |
