Flavonoid metabolites reduce tumor necrosis factor-α secretion to a greater extent than their precursor compounds in human THP-1 monocytes.

Scope: Flavonoids are generally studied in vitro, in isolation, and as unmetabolized precursor structures. However, in the habitual diet, multiple flavonoids are consumed together and found present in the circulation as complex mixtures of metabolites. Using a unique study design, we investigated the potential for singular or additive anti-inflammatory effects of flavonoid metabolites relative to their precursor structures.

Nuclear receptor-binding protein 1: a novel tumour suppressor and pseudokinase.

Pseudokinases are a class of kinases which are structurally designated as lacking kinase activity. Despite the lack of kinase domain sequence conservation, there is increasing evidence that a number of pseudokinases retain kinase activity and/or have critical cellular functions, casting aside previous notions that pseudokinases simply exist as redundant kinases. Moreover, a number of recent studies have implicated pseudokinases as critical components in cancer formation and progression.

Differential regulation of chemotaxis: role of Gβγ in chemokine receptor-induced cell migration.

CC and CXC chemokine receptor signalling networks are regulated in different ways. Here we show that intracellular calcium release and cell migration occur independent of Gβγ activation in response to CCL3, whereas CXCL11 induced migration of activated T-lymphocytes depends on Gβγ activation. Treatment of a range of cell types with gallein, a pharmacological inhibitor of Gβγ signalling, did not result in a reduction in CCL3 induced cellular migration, but resulted in enhanced calcium mobilisation following chemokine stimulation.

Avidity-based extracellular interaction screening (AVEXIS) for the scalable detection of low-affinity extracellular receptor-ligand interactions.

Extracellular protein:protein interactions between secreted or membrane-tethered proteins are critical for both initiating intercellular communication and ensuring cohesion within multicellular organisms. Proteins predicted to form extracellular interactions are encoded by approximately a quarter of human genes, but despite their importance and abundance, the majority of these proteins have no documented binding partner. Primarily, this is due to their biochemical intractability: membrane-embedded proteins are difficult to solubilise in their native conformation and contain structurally-important posttranslational modifications.

CCR5 internalisation and signalling have different dependence on membrane lipid raft integrity.

The chemokine receptor, CCR5, acts as a co-receptor for human immunodeficiency virus entry into cells. CCR5 has been shown to be targeted to cholesterol- and sphingolipid-rich membrane microdomains termed lipid rafts or caveolae. Cholesterol is essential for CCL4 binding to CCR5 and for keeping the conformational integrity of the receptor.