High impact information on PASK

• This interaction is regulated by the PAS kinase PAS domain, raising the possibility that this interaction (and phosphorylation event) is modulated by the cellular metabolic state [1].
• Efficient phosphorylation requires a region of PAS kinase outside the catalytic domain [1].
• Demonstrating a physiological role for PASK activation, comicroinjection into clonal beta cells of cDNA encoding wild-type PASK, or PASK protein itself, mimics the induction of preproinsulin promoter activity by high glucose concentrations [2].
• Here, we show that elevated glucose concentrations rapidly increase PASK activity in pancreatic islet beta cells, an event followed by the accumulation of both PASK mRNA and protein [2].
• We conclude that PASK is an important metabolic sensor in nutrient-sensitive mammalian cells and plays an unexpected role in the regulation of key genes involved in maintaining the differentiated phenotype of pancreatic beta cells [2].

Biological context of PASK

• The amino acid sequence of PASK specifies two PAS domains followed by a canonical serine/threonine kinase domain, indicating that it might represent the first mammalian PAS-regulated protein kinase [3].
• Isolation and expression of PASK, a serine/threonine kinase, during rat embryonic development, with special emphasis on the pancreas [4].
• Although the PAS domain of the mammalian PAS kinase (PASK) is closely related to the bacterial oxygen sensor FixL, it is unclear whether PASK activity is changed in mammalian cells in response to nutrients and might therefore contribute to signal transduction by these or other stimuli [2].
• The human PASKIN and mouse Paskin genes show a conserved intron-exon structure and share their promoter regions with another ubiquitously expressed gene that encodes a regulator of protein phosphatase-1 [5].
• A similar view has been presented for the Tammar wallaby, where formation of a scrotum, or a pouch, is a direct consequence of the presence/absence of two X chromosomes (Pask and Renfree, 2001) [6].

Anatomical context of PASK

• PASK was widely expressed in rat tissues but negligible in liver and skeletal muscle [7].
• Subcellular fractionation showed that PASK was present in both the cytosol and the Triton X-100-insoluble cytoskeletal fraction in brain [7].
• Immunohistochemical analysis revealed that PASK was localized to a distinct set of cells including neurons, adrenal glomerulosa cells, and transporting epithelia such as epithelial cells of brain choroid plexus, distal tubule and collecting duct of kidney, duct of salivary gland, and parietal cells of stomach [7].
• We previously identified two PAS proteins highly expressed in the testis: a novel isoform of the hypoxia-inducible factor (HIF)-1alpha and PASKIN, a PAS-Ser/Thr kinase related to bacterial oxygen sensing PAS-domain proteins [8].
• The potential for any morphological part of a photoreceptor cell to function as an optical waveguide is determined 1) by the dimensionless parameter V as shown by Snyder (IEEE Trans., Microwave Theory Tech. 17: 1133, 1969) and by Snyder, Pask and Mitchell (J [9].

Associations of PASK with chemical compounds

• We further demonstrate that the N-terminal PAS domain is a cis regulator of PASK catalytic activity [3].
• PAS kinase: an evolutionarily conserved PAS domain-regulated serine/threonine kinase [3].

Enzymatic interactions of PASK

• Phosphopeptide mapping showed that insulin-dependent in vivo sites of IRS-1 serine phosphorylation were comparable to those of PAS kinase phosphorylated IRS-1 [10].

Other interactions of PASK

• Overexpression of wild type PASK causes a small (sNKCC1 22 +/- 8% p < 0.05, hNKCC1 12 +/- 3% p < 0.01) but significant increase in shark and human cotransporter activity in HEK cells [11].
• Here we report that IRS-1 is phosphorylated by a wortmannin insensitive phosphatidylinositol 3'-kinase (PI 3-kinase)-associated serine kinase (PAS kinase) distinct from PI 3-kinase serine kinase [10].

References