Heidi C. E. Welch

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Rac, a member of the Rho family of monomeric GTPases, is an integrator of intracellular signaling in a wide range of cellular processes. We have purified a PtdIns(3,4,5)P3-sensitive activator of Rac from neutrophil cytosol. It is an abundant, 185 kDa guanine-nucleotide exchange factor (GEF), which we cloned and named P-Rex1. The recombinant enzyme has(More)
Rac GTPases regulate cytoskeletal structure, gene expression, and reactive oxygen species (ROS) production. Rac2-deficient neutrophils cannot chemotax, produce ROS, or degranulate upon G protein-coupled receptor (GPCR) activation. Deficiency in PI3Kgamma, an upstream regulator of Rac, causes a similar phenotype. P-Rex1, a guanine-nucleotide exchange factor(More)
typically possess a PH domain that can bind the lipid and drive translocation of the host protein to the site of PtdIns(3,4,5)P 3 accumulation Summary in the plasma membrane (not all PH domains bind PtdIns(3,4,5)P 3 ; Lemmon and Ferguson, 2000). In many Rac, a member of the Rho family of monomeric cells, type 1 PI3Ks have been shown to be necessary GTPases,(More)
The small G protein family Rac has numerous regulators that integrate extracellular signals into tight spatiotemporal maps of its activity to promote specific cell morphologies and responses. Here, we have generated a mouse strain, Rac-FRET, which ubiquitously expresses the Raichu-Rac biosensor. It enables FRET imaging and quantification of Rac activity in(More)
The small GTPase Rac controls cell morphology, gene expression, and reactive oxygen species formation. Manipulations of Rac activity levels in the cerebellum result in motor coordination defects, but activators of Rac in the cerebellum are unknown. P-Rex family guanine-nucleotide exchange factors activate Rac. We show here that, whereas P-Rex1 expression(More)
BACKGROUND Blood platelets undergo a carefully regulated change in shape to serve as the primary mediators of hemostasis and thrombosis. These processes manifest through platelet spreading and aggregation and are dependent on platelet actin cytoskeletal changes orchestrated by the Rho GTPase family member Rac1. To elucidate how Rac1 is regulated in(More)
The P-Rex family of guanine-nucleotide exchange factors (GEFs) are activators of the small GTPase Rac (Donald et al., 2004; Rosenfeldt et al., 2004; Welch et al., 2002). They are directly regulated in vitro and in vivo by the lipid second messenger phosphatidylinositol (3,4,5)-triphosphate (PtdIns(3,4,5)P3) and by the betagamma subunits of heterotrimeric G(More)
P-Rex1 is a guanine-nucleotide exchange factor (GEF) that activates the small G protein (GTPase) Rac1 to control Rac1-dependent cytoskeletal dynamics, and thus cell morphology. Three mechanisms of P-Rex1 regulation are currently known: (i) binding of the phosphoinositide second messenger PIP3, (ii) binding of the Gβγ subunits of heterotrimeric G proteins,(More)
Coming early to the late genes Ira Herskowitz When I was an undergraduate at Caltech, I worked in Bob Edgar's laboratory on an obscure aspect of phage T4 morphogenesis, which had previously been studied by a little-known South African geneticist, Sydney Brenner [1]. I remember a journal club presented by one of the graduate students in the lab, about the(More)
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