Rho‐specific binding and guanine nucleotide exchange catalysis by KIAA0380, a Dbl family member

Rümenapp, Ulrich; Blomquist, Andrea; Schwörer, Guntram; Schablowski, Helge; Psoma, Amalia; Jakobs, Karl H.

doi:10.1016/s0014-5793(99)01270-3

Cited by 52 publications

(52 citation statements)

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“…In particular, 15 Dbl-related exchange factors active on RhoA have been characterized so far, that have ubiquitous or tissue speci®c expression patterns and that can activate only RhoA or several Rho GTPases: GEF720 (this work), p114Rho-GEF (Blomquist et al, 2000), KIAA380/PDZ-Rho-GEF (Fukuhara et al, 1999;Rumenapp et al, 1999), GEF337 ( De Toledo et al, 2000), p115RhoGEF/Lsc Figure 4 GEF720 induces RhoA dependent stress ®ber assembly in ®broblasts. REF52 cells were transfected with constructs expressing myc-tagged RhoA-V14 (a) or GEF720 (c,e) and GFP-tagged KID2 (g), actin was visualized with TRITC-phalloidin (b,d,f).…”

Section: Discussionmentioning

confidence: 95%

“…GEF720 is divergent from the other GEFs characterized so far: the closest known mammalian Dblrelated proteins are p115RhoGEF/Lsc (Glaven et al, 1996;Kozasa et al, 1998) and KIAA380/PDZRhoGEF (Fukuhara et al, 1999;Rumenapp et al, 1999) and there are no known homologues of GEF720 in other organisms such as Drosophila or C. elegans. The DH domain of GEF720 is only 33 and 28% identical to that of p115-and PDZRhoGEF respectively and the PH domain 21% and 19% identical respectively (Figure 2a), while p115RhoGEF, Lsc and PDZ-RhoGEF DH domains are more than 50% identical (Fukuhara et al, 1999).…”

Section: Kiaa0720 Encodes Gef720 a Dbl Related Proteinmentioning

confidence: 99%

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The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2–1p36.3.

et al. 2001

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Section: Discussionmentioning

confidence: 95%

Section: Kiaa0720 Encodes Gef720 a Dbl Related Proteinmentioning

confidence: 99%

The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2–1p36.3.

et al. 2001

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“…1A,J). Notably, a similar construct has been reported to block G protein-coupled activation of RhoA in mammalian cell culture (Rumenapp et al, 1999). This construct presumably acts as a competitive inhibitor of the endogenous protein through its binding to upstream components and inability to activate Rho.…”

Section: Research Article Development 134 (5)mentioning

confidence: 97%

“…After serum starvation, cultured HEK293 cells transfected with human ARHGEF11 develop actin stress fibers as a result of RhoA stimulation (Rumenapp et al, 1999). We predicted that zebrafish Arhgef11 acts similarly owing to the conservation of crucial amino acids within the DH domain required for Rho specificity (see Fig.…”

Section: Arhgef11 Induces Actin Stress Fiber Formation In Cultured Cellsmentioning

confidence: 99%

New functions for a vertebrate Rho guanine nucleotide exchange factor in ciliated epithelia

et al. 2007

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Human ARHGEF11, a PDZ-domain-containing Rho guanine nucleotide exchange factor (RhoGEF), has been studied primarily in tissue culture, where it exhibits transforming ability, associates with and modulates the actin cytoskeleton, regulates neurite outgrowth, and mediates activation of Rho in response to stimulation by activated Gα12/13 or Plexin B1. The fruit fly homolog, RhoGEF2, interacts with heterotrimeric G protein subunits to activate Rho, associates with microtubules, and is required during gastrulation for cell shape changes that mediate epithelial folding. Here, we report functional characterization of a zebrafish homolog of ARHGEF11 that is expressed ubiquitously at blastula and gastrula stages and is enriched in neural tissues and the pronephros during later embryogenesis. Similar to its human homolog,zebrafish Arhgef11 stimulated actin stress fiber formation in cultured cells,whereas overexpression in the embryo of either the zebrafish or human protein impaired gastrulation movements. Loss-of-function experiments utilizing a chromosomal deletion that encompasses the arhgef11 locus, and antisense morpholino oligonucleotides designed to block either translation or splicing, produced embryos with ventrally-curved axes and a number of other phenotypes associated with ciliated epithelia. Arhgef11-deficient embryos often exhibited altered expression of laterality markers, enlarged brain ventricles, kidney cysts, and an excess number of otoliths in the otic vesicles. Although cilia formed and were motile in these embryos, polarized distribution of F-actin and Na+/K+-ATPase in the pronephric ducts was disturbed. Our studies in zebrafish embryos have identified new, essential roles for this RhoGEF in ciliated epithelia during vertebrate development.

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“…RhoGEF activates Rho GTPases (30,31). Thus, modular domains of RGS proteins may act as scaffolds to recruit specific classes of signaling proteins or alternatively as motifs that target these molecules to specific subcellular compartments.…”

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confidence: 99%

Mechanisms Governing Subcellular Localization and Function of Human RGS2

Heximer

Lim

Bernard

et al. 2001

Journal of Biological Chemistry

118

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RGS proteins negatively regulate heterotrimeric G proteins at the plasma membrane. RGS2-GFP localizes to the nucleus, plasma membrane, and cytoplasm of HEK293 cells. Expression of activated G q increased RGS2 association with the plasma membrane and decreased accumulation in the nucleus, suggesting that signal-induced redistribution may regulate RGS2 function. Thus, we identified and characterized a conserved N-terminal domain in RGS2 that is necessary and sufficient for plasma membrane localization. Mutational and biophysical analyses indicated that this domain is an amphipathic ␣-helix that binds vesicles containing acidic phospholipids. However, the plasma membrane targeting function of the amphipathic helical domain did not appear to be essential for RGS2 to attenuate signaling by activated G q . Nevertheless, truncation mutants indicated that the N terminus is essential, potentially serving as a scaffold that binds receptors, signaling proteins, or nuclear components. Indeed, the RGS2 N terminus directs nuclear accumulation of GFP. Although RGS2 possesses a nuclear targeting motif, it lacks a nuclear import signal and enters the nucleus by passive diffusion. Nuclear accumulation of RGS2 does not limit its ability to attenuate G q signaling, because excluding RGS2 from the nucleus was without effect. RGS2 may nonetheless regulate signaling or other processes in the nucleus.Many hormones, neurotransmitters, and sensory stimuli elicit specific physiological responses in target tissues by activating receptors that are coupled to heterotrimeric G proteins 1 (1, 2). Activated receptors promote exchange of GTP for GDP on G␣ subunits leading to dissociation of GTP-bound G␣ subunits from G␤␥ heterodimers and activation of downstream effector pathways. Signals are terminated following G␣-catalyzed hydrolysis of GTP and reformation of G protein heterotrimers. Thus, G proteins act as molecular switches to coordinate the wide range of responses elicited by extracellular stimuli.The regulators of G protein signaling (RGS) proteins are a large family that regulate G protein signaling in part by acting as GTPase-activating proteins (GAPs) for several classes of G protein ␣ subunits (3-6). The GAP activity of RGS proteins shortens the half-life of active, GTP-bound G␣ subunits and leads to attenuation of a response during prolonged stimulation or accelerated termination of the signal following removal of agonist (7-11). Binding of RGS proteins to active G␣ subunits can also interfere with effector binding, thereby blocking activation and downstream signaling (12). These activities are mediated by the ϳ120-amino acid RGS domain, a conserved feature of this protein family.Genetic studies in budding yeast (13) and Caenorhabditis elegans (14) indicate that eukaryotes express several types of RGS proteins to provide selective regulation of distinct G protein signaling pathways, and a means of differentially regulating a single pathway in response to various physiologic conditions. Similarly, certain mammalian RGS proteins have b...

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Rho‐specific binding and guanine nucleotide exchange catalysis by KIAA0380, a Dbl family member

Cited by 52 publications

References 20 publications

The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2–1p36.3.

The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2–1p36.3.

New functions for a vertebrate Rho guanine nucleotide exchange factor in ciliated epithelia

Mechanisms Governing Subcellular Localization and Function of Human RGS2

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