TABLE 4.
SGK3 and glucose, amino acid, and other substance transport.
| Cell type | Target | Result | Related disease |
|---|---|---|---|
| Xenopus oocytes and jejunum epithelial cells | SGLT1 | In vitro, SGK3 could increase the SGLT1 activity by phosphorylating Nedd4-2 and accelerate glucose absorption. In vivo, compared with SGK3 wild-type mice, the SGLT1 function and intestinal glucose transport of SGK3 knockout mice were impaired | Diabetes and obesity |
| Xenopus oocytes | SLC6A19 and Nedd4-2 | SGK3 stimulated SLC6A19 activity and expression by influencing the ubiquitin ligase Nedd4-2 independently of 100Ser without modifying carrier substrate affinities | |
| Xenopus oocytes | ASCT2 | SGK3 could up-regulate the expression and activity of ASCT2, thereby regulating the absorption of cellular nutrients | |
| Xenopus oocytes and murine hippocampal neurones | GluR1 | SGK3 can up-regulate the GluR1 expression and activity in neuronal synapses and promote the transport of glutamate | |
| Xenopus oocytes | GluR6 | SGK3 could also up-regulate the activity of GluR6, maintaining neuronal excitability and memory consolidation | |
| Xenopus oocytes | EAAT1, EAAT2, EAAT4, and EAAT5 | SGK3 can stimulate the expression of excitatory amino acid transporters (EAAT1, EAAT2, EAAT4, and EAAT5) and contribute to glutamate uptake | Loss of EAAT function and accumulation of glutamate is closely related to intractable temporal lobe epilepsy (TLE), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), glaucoma, and diabetic retinopathy |
| Xenopus oocytes | SN1 (SLC38A3/SNAT3) and Nedd4-2 | SGK3 can reverse the inhibition of SN1 by Nedd4-2 through phosphorylation and inhibition of Nedd4-2 | Mice deficient of SN1 can cause ataxia and disorders in amino acid homeostasis and glucose metabolism |
| Xenopus oocytes | CreaT and SLC6A8 | SGK3 was a potent positive regulator of CreaT, which might regulate the creatine uptake | CreaT defect could lead to seizures, intellectual disability, and language disorders |
| Xenopus oocytes | NaDC1 | SGK3 could enhance the activity of NaDC1, promoting renal tubular reabsorption of citrate | Promoting the occurrence of calcium urolithiasis |