Stabilization of interdomain interactions in G protein α subunits as a determinant of Gα subtype signaling specificity.

Highly homologous members of the Gα family, Gα, have distinct tissue distributions and physiological functions, yet their biochemical and functional properties are very similar. We recently identified PDZ-RhoGEF (PRG) as a novel Gα effector that is poorly activated by Gα. In a proteomic proximity labeling screen we observed a strong preference for Gα relative to Gα with respect to engagement of a broad range of potential targets.

Stabilization of Interdomain Interactions in G protein α Subunits Determines Gα Subtype Signaling Specificity.

Highly homologous members of the Gα family, Gα, have distinct tissue distributions and physiological functions, yet the functional properties of these proteins with respect to GDP/GTP binding and regulation of adenylate cyclase are very similar. We recently identified PDZ-RhoGEF (PRG) as a novel Gα effector, however, it is poorly activated by Gα. Here, in a proteomic proximity labeling screen we observed a strong preference for Gα relative to Gα with respect to engagement of a broad range of potential targets.

A naturally occurring membrane-anchored Gα variant, XLα, activates phospholipase Cβ4.

Extra-large stimulatory Gα (XLα) is a large variant of G protein α subunit (Gα) that uses an alternative promoter and thus differs from Gα at the first exon. XLα activation by G protein-coupled receptors mediates cAMP generation, similarly to Gα; however, Gα and XLα have been shown to have distinct cellular and physiological functions. For example, previous work suggests that XLα can stimulate inositol phosphate production in renal proximal tubules and thereby regulate serum phosphate levels.

A network of Gα signaling partners is revealed by proximity labeling proteomics analysis and includes PDZ-RhoGEF.

G protein–coupled receptors (GPCRs) that couple to the Gα family of G proteins are key regulators of cell and tissue physiology. Our previous work has revealed new roles for Gα in regulating the migration of neutrophils and fibrosarcoma cells downstream of activated chemoattractant receptors. Here, we used an intact cell proximity–based labeling coupled to tandem mass tag (TMT)–based quantitative proteomics analysis to identify proteins that selectively interacted with the GTP-bound form of Gα.

Epigenetic regulation of arginine vasopressin receptor 2 expression by PAX2 and Pax transcription interacting protein.

Renal arginine vasopressin receptor 2 (AVPR2) plays a crucial role in osmoregulation. Engagement of ligand with AVPR2 results in aquaporin 2 movement to the apical membrane and water reabsorption from the urinary filtrate. Despite this essential role, little is known about transcriptional regulation of .

Pax2 and Pax8 Proteins Regulate Urea Transporters and Aquaporins to Control Urine Concentration in the Adult Kidney.

Background: As the glomerular filtrate passes through the nephron and into the renal medulla, electrolytes, water, and urea are reabsorbed through the concerted actions of solute carrier channels and aquaporins at various positions along the nephron and in the outer and inner medulla. Proliferating stem cells expressing the nuclear transcription factor Pax2 give rise to renal epithelial cells. Pax2 expression ends once the epithelial cells differentiate into mature proximal and distal tubules, whereas expression of the related Pax8 protein continues.

HNF1A is a novel oncogene that regulates human pancreatic cancer stem cell properties.

The biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a human PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, decreased PCSC marker expression, and downregulation of expression.

Landscape genetics and population structure in Valley Oak (Quercus lobata Née).

Premise Of The Study: Although long-distance pollen movement is common in wind-pollinated trees, barriers to gene flow may occur in species that have discontinuous ranges or are confined to certain habitat types. We investigated the genetic structure of Quercus lobata Née populations throughout much of their range in California. We assessed the connectivity of populations and determined if barriers to gene flow occurred, and if so, if they corresponded to landscape features.

The Groucho-associated phosphatase PPM1B displaces Pax transactivation domain interacting protein (PTIP) to switch the transcription factor Pax2 from a transcriptional activator to a repressor.

Pax genes encode developmental regulatory proteins that specify cell lineages and tissues in metazoans. Upon binding to DNA through the conserved paired domain, Pax proteins can recruit both activating and repressing complexes that imprint distinct patterns of histone methylation associated with either gene activation or silencing. How the switch from Pax-mediated activation to repression is regulated remains poorly understood.

Screening for asymptomatic atrial fibrillation while monitoring the blood pressure at home: trial of regular versus irregular pulse for prevention of stroke (TRIPPS 2.0).

Asymptomatic atrial fibrillation (AF) is a common cause of strokes. Physician screening for AF has been recommended. Home screening for AF may increase the likelihood of detecting asymptomatic AF in patients at risk for stroke because of AF.