Lack of beta-arrestin signaling in the absence of active G proteins.

G protein-independent, arrestin-dependent signaling is a paradigm that broadens the signaling scope of G protein-coupled receptors (GPCRs) beyond G proteins for numerous biological processes. However, arrestin signaling in the collective absence of functional G proteins has never been demonstrated. Here we achieve a state of "zero functional G" at the cellular level using HEK293 cells depleted by CRISPR/Cas9 technology of the Gs/q/12 families of Gα proteins, along with pertussis toxin-mediated inactivation of Gi/o.

The Orphan Receptor GPR17 Is Unresponsive to Uracil Nucleotides and Cysteinyl Leukotrienes.

Pairing orphan G protein–coupled receptors (GPCRs) with their cognate endogenous ligands is expected to have a major impact on our understanding of GPCR biology. It follows that the reproducibility of orphan receptor ligand pairs should be of fundamental importance to guide meaningful investigations into the pharmacology and function of individual receptors. GPR17 is an orphan receptor characterized by some as a dualistic uracil nucleotide/cysteinyl leukotriene receptor and by others as inactive toward these stimuli altogether.

Coumarin modulates the cell-cycle progression of an MTV-EJras cell line.

The effects of coumarin (1,2-benzopyrone) on ras oncogene expression during the cell cycle of an MTV-EJras cell line was determined by flow cytometry. ras oncogene expression in cells was induced by dexamethasone and increased fivefold during G1/G0 phase and threefold in S phase. Dexamethasone also increased the percentage of cells in S phase from 21% to 31%, compared to phosphate-buffered-saline-treated control cells (P < 0.

Increased natural killer cell activity correlates with low or negative expression of the HER-2/neu oncogene in patients with breast cancer.

Background: Increased expression of the HER-2/neu oncogene in breast cancer correlates with decreased estrogen receptor concentration and seems to be an important prognostic factor. The authors investigated whether there is a correlation between HER-2/neu expression and immunologic parameters representing tumor defense in patients with breast cancer.

Method: A Western blot analysis was used to investigate HER-2/neu expression, whereas a chromium-release assay using the K562 cell line as target was used to measure natural killer (NK) cell activity.

Coexpression of HER-2/neu and p53 is associated with a shorter disease-free survival in node-positive breast cancer patients.

Breast cancer tissue was examined for overexpression of HER-2/neu and p53 oncogene proteins. Samples from 105 breast cancer patients were investigated by Western-blot analysis and their relationship to other established markers and clinical outcome was examined. In 21.