Table 1.

Data supporting a direct association of IRS-1 and mTOR with PP2A

1	Analysis of IRS-1 using motif prediction software (MOTIF, which encompasses 6 different databases including PROSITE, PFAM, and other databases) shows the presence of signatures corresponding to ankyrin-repeat motifs involved in protein-protein interactions. Such repeats are found in protein phosphatase PP1 regulatory subunits in cardiomyocytes.
2	PP2A has been shown to modulate potassium channels in cardiomyocytes through AT2R and glycogen synthase kinase (GSK-3) signaling.
3	Ang II has been shown to activate PP2A through AT2R signaling.
4	The scaffolding unit of PP2A contains TOR repeats, which are similar to mTOR.
5	IRS-1 co-immunoprecipitates with the mTOR scaffolding protein Raptor, and mTOR may modulate IRS-1 degradation via its complexing with PP2A.
6	Protein phosphatase PP2A activity can be inhibited by PI3K signaling in hepatocytes.
7	The putative mTOR direct phosphorylation (binding?) motif at serine 636/639 of IRS-1 is in a structurally ordered region of the protein (followed immediately by a short disordered region), which may allow stable binding of the mTOR-Raptor scaffold-PP2A scaffold complex.
8	The catalytic subunit of PP2A has been shown to bind alpha4 docking protein (the yeast TAP42 homologue); mTOR is able to phosphorylate this complex and therefore inactivate it (unknown which component). This process restrains the phosphatases and their effects on S6K1 phosphorylation/activation and capping protein 4E-BP.