351 research outputs found
Rap1, a mercenary among the Ras-like GTPases
AbstractThe small Ras-like GTPase Rap1 is an evolutionary conserved protein that originally gained interest because of its capacity to revert the morphological phenotype of Ras-transformed fibroblasts. Rap1 is regulated by a large number of stimuli that include growth factors and cytokines, but also physical force and osmotic stress. Downstream of Rap1, a plethora of effector molecules has been proposed on the basis of biochemical studies. Here, we present an overview of genetic studies on Rap1 in various model organisms and relate the observed phenotypes to in vitro studies. The picture that emerges is one in which Rap1 is a versatile regulator of morphogenesis, by regulating diverse processes that include establishment of cellular polarity, cell–matrix interactions and cell–cell adhesion. Surprisingly, genetic experiments indicate that in the various model organisms, Rap1 uses distinct effector molecules that impinge upon the actin cytoskeleton and adhesion molecules
Differential fMet-Leu-Phe- and Platelet-activating Factor-induced Signaling Toward Ral Activation in Primary Human Neutrophils
We have measured the activation of the small GTPase
Ral in human neutrophils after stimulation with fMet-
Leu-Phe (fMLP), platelet activating factor (PAF), and
granulocyte macrophage-colony stimulating factor and
compared it with the activation of two other small
GTPases, Ras and Rap1. We found that fMLP and PAF,
but not granulocyte macrophage-colony stimulating factor,
induce Ral activation. All three stimuli induce the
activation of both Ras and Rap1. Utilizing specific inhibitors
we demonstrate that fMLP-induced Ral activation
is mediated by pertussis toxin-sensitive G-proteins and
partially by Src-like kinases, whereas fMLP-induced
Ras activation is independent of Src-like kinases. PAFinduced
Ral activation is mediated by pertussis toxininsensitive
proteins, Src-like kinases and phosphatidylinositol
3-kinase. Phosphatidylinositol 3-kinase is not
involved in PAF-induced Ras activation. The calcium
ionophore ionomycin activates Ral, but calcium depletion
partially inhibits fMLP- and PAF-induced Ral activation,
whereas Ras activation was not affected. In addition,
12-O-tetradecanoylphorbol-13-acetate-induced
activation of Ral is completely abolished by inhibitors of
protein kinase C, whereas 12-O-tetradecanoylphorbol-
13-acetate-induced Ras activation is largely insensitive.
We conclude that in neutrophils Ral activation is mediated
by multiple pathways, and that fMLP and PAF induce
Ral activation differently
"Rondeel" beter voor burger, boer en beestje
Rondeel dóet niet aan maatschappelijk verantwoord ondernemen, Rondeel Ãs maatschappelijk verantwoord ondernemen, volgens zijn initiatiefnemers. Binnenkort kan iedereen kennis nemen van het concept. Op 8 april wordt de eerste Rondeel-houderij voor leghennen in Barneveld feestelijk geopend door Gerda Verburg, demissionair minister van LNV
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