Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8.

Phosphate (Pi) serves countless metabolic pathways and is involved in macromolecule synthesis, energy storage, cellular signaling, and bone maintenance. Herein, we describe the coordination of Pi uptake and efflux pathways to maintain mammalian cell Pi homeostasis. We discover that XPR1, the presumed Pi efflux transporter, separately supervises rates of Pi uptake.

X-ray crystallographic analyses of 14 IPMK inhibitor complexes.

Inositol polyphosphate multikinase (IPMK) is a ubiquitously expressed kinase that has been linked to several cancers. Here, we report 14 new co-crystal structures (1.7Å - 2.

Drosophila cytokine GBP2 exerts immune responses and regulates GBP1 expression through GPCR receptor Mthl10.

Growth-blocking peptide (GBP), an insect cytokine, was first found in armyworm Mythimna separata. A functional analogue of GBP, stress-responsive peptide (SRP), was also identified in the same species. SRP gene expression has been demonstrated to be enhanced by GBP, indicating that both cytokines are organized within a hierarchical regulatory network.

Biochemical and structural characterization of an inositol pyrophosphate kinase from a giant virus.

Kinases that synthesize inositol phosphates (IPs) and pyrophosphates (PP-IPs) control numerous biological processes in eukaryotic cells. Herein, we extend this cellular signaling repertoire to viruses. We have biochemically and structurally characterized a minimalist inositol phosphate kinase (i.

IP8: A quantitatively minor inositol pyrophosphate signaling molecule that punches above its weight.

The inositol pyrophosphates (PP-IPs) are specialized members of the wider inositol phosphate signaling family that possess functionally significant diphosphate groups. The PP-IPs exhibit remarkable functionally versatility throughout the eukaryotic kingdoms. However, a quantitatively minor PP-IP - 1,5 bisdiphosphoinositol tetrakisphosphate (1,5-IP) - has received considerably less attention from the cell signalling community.