The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras's ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling syste...

Signaling by the BCR involves activation of several members of the Ras superfamily of small GTPases, among which is Ras itself. Ras can control the activity of multiple effectors, including Raf, PI3K, and guanine nucleotide exchange factors for the small GTPase Ral. Ras, Raf, and PI3K have been implicated in a variety of processes underlying B cell development, differentiation, and function; ho...

The Ras superfamily of GTP-binding proteins (> 50 members) regulates a diverse spectrum of intracellular processes. These include cellular proliferation and differentiation, intracellular vesicular trafficking, cytoskeletal control, NADPH oxidase function, as well as others. In this review, we describe recent progress and emerging themes in the action and regulation of these important cellular ...

The physiological effects of many extracellular stimuli are mediated by receptor-promoted activation of phospholipase C (PLC) and consequential activation of inositol lipid-signaling pathways. These signaling responses include the classically described conversion of PtdIns(4,5)P(2) to the Ca(2+)-mobilizing second messenger Ins(1,4,5)P(3) and the protein kinase C-activating second messenger diac...

To date phylogeny has been used to compare entire families of proteins based on their nucleotide or amino acid sequence. Here we developed a novel analytical platform allowing a systematic comparison of protein families based on their biochemical properties. This approach was validated on the Rho subfamily of GTPases. We used two high throughput methods, referred to as AlphaScreen and FlashPlat...

OBJECTIVES Hypoxia or exposure to excessive reactive oxygen or nitrogen species could induce S-nitrosylation of various target proteins, including GTPases of the Ras-superfamily. Under hypoxic conditions, the Ras-protein is translocated to the cytosol and interacts with the Golgi complex, endoplasmic reticulum, mitochondria. The mobility/translocation of Ras depend on the cells oxidative status...

An approach involving microinjection and microanalysis has been developed to investigate signal-transduction pathways involved in the hormonal control of metabolism. We have applied this strategy to investigate the role of Ras signaling in the acute activation of glucose transport by insulin in cardiac myocytes. Glucose transport activity was assessed by measuring the initial rate of accumulati...

Introduction The Center for International Meetings on Biology workshop on ‘Exchange Factors’ provided an up-to-date view of how guaninenucleotide-exchange factors (GEFs) affect the biochemical pathways that regulate the Ras superfamily of small GTPases, and how these molecules function as part of an interrelated network of regulatory proteins that mediate the biological responses of Ras-like GT...

Aberrant activation of the Ras/ERK pathway mediates breast cancer initiation and aggressiveness. Therefore, it is important to identify miRNAs that modulate the Ras/ERK pathway during breast carcinogenesis and progression. The Ras GTPase superfamily member RERG (Ras-related and estrogen-regulated growth inhibitor) acts as a tumor suppressor to reduce breast cancer cell proliferation and tumor f...

A large superfamily (> 50 members) of monomeric GTPbinding proteins structurally related to the ras oncogene proteins has been described in the past few years (Bourne et al., 1991; Grand and Owen, 1991; Hall, 1990; Valencia et al., 1991). These proteins have been implicated in the regulation of a diverse array of cellular processes, utilizing their ability to bind and hydrolyse GTP as a means t...