TABLE 2.
Phenotypes associated with PAS kinase in yeast, mice, and man
| Organism | Genotype | Growth conditions | Phenotypes | Study |
|---|---|---|---|---|
| S. cerevisiae | psk1− psk2− | Galactose, 39 °C Glucose (log and SP) |
Growth inhibition Glycogen hyperaccumulation Trehalose hyperaccumulation |
(37) |
| psk2− | Galactose, 39 °C Glucose (log and SP) |
Limited growth Intermediate glycogen hyperaccumulation Intermediate trehalose hyperaccumulation |
(37) | |
| psk1− | Glucose (log and SP) | Intermediate glycogen hyperaccumulation Intermediate trehalose hyperaccumulation |
(37) | |
| PSK2OEstm1− | Glucose, 37 °C | Rescues growth of stm1− mutant | (37) | |
| psk2−rom2− | Glucose, 37 °C | Exacerbates growth of rom2ts mutant | (22) | |
| PSK2OEtor2ts | Glucose, 37 °C | Overexpression rescues tor2ts | (42) | |
| PSK2OEUGP1OE | Galactose, 37 °C | Overexpression rescues UGP1OE toxicity | (39,48) | |
|
| ||||
| M. musculus | pask−/− | 16 H fasting Glucose (10 mM) Insulin (20 mM) |
Increased fasting plasma glucose and glucagon Impaired inhibition of glucagon secretion Decreased islet and whole pancreas insulin Increased glucagon secretion |
(25) |
| hPASKOE | Glucose (1 mM) | Inhibited glucagon release in TC1–9 islets | (25) | |
| pask−/− | Glucose (1 mM) | Constitutive glucagon release in TC1–9 islets | (25) | |
| pask−/− | Glucose (1mM) High fat diet (45%) |
Decreased insulin levels Glucose tolerant Insulin sensitive Less weight gain Hypermetabolic (higher O2 consumption, CO2 production and heat generation) Reduced liver triglyceride accumulation Increased ATP production |
(30) | |
| pask−/− | Acute hypoxia | Higher hypoxic ventilatory response | (31) | |
| hPASK(KD)OE | Decreased intracellular insulin in TC1–9 cells | (25) | ||
| hPASK G1117E | Hyperinsulin secretion in CD1 islets | (28) | ||
|
| ||||
| H. Sapiens | hPASK G1117E | MODY associated | (28) | |
Log is log/exponential phase, SP is stationary phase, OE is overexpression and MODY is Maturity-Onset Diabetes of the Young.