<i>Ras</i>‐related genes in <i>Dictyostelium discoideum</i>

Robbins, Stephen M.; Khosla, Meenal; Thiéry, Richard; Spiegelman, George B.

doi:10.1002/dvg.1020120123

Cited by 10 publications

(4 citation statements)

References 38 publications

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“…Rap proteins are small GTPases from the Ras family, and genes encoding them are highly conserved across species (1)(2)(3)(4). Genetic analysis of Rap1 function in lower eukaryotes has revealed that Rap is critical for development, as loss-of-function mutations are lethal in Drosophila (3) and Dictyostelium (5).…”

Section: Introductionmentioning

confidence: 99%

Rap1b is required for normal platelet function and hemostasis in mice

Smyth²,

et al. 2005

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Rap1b, an abundant small GTPase in platelets, becomes rapidly activated upon stimulation with agonists. Though it has been implicated to act downstream from G protein-coupled receptors (GPCRs) and upstream of integrin α IIb β 3 , the precise role of Rap1b in platelet function has been elusive. Here we report the generation of a murine rap1b knockout and show that Rap1b deficiency results in a bleeding defect due to defective platelet function. Aggregation of Rap1b-null platelets is reduced in response to stimulation with both GPCR-linked and GPCR-independent agonists. Underlying the defective Rap1b-null platelet function is decreased activation of integrin α IIb β 3 in response to stimulation with agonists and signaling downstream from the integrin α IIb β 3 . In vivo, Rap1b-null mice are protected from arterial thrombosis. These data provide genetic evidence that Rap1b is involved in a common pathway of integrin activation, is required for normal hemostasis in vivo, and may be a clinically relevant antithrombotic therapy target.

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Section: Introductionmentioning

confidence: 99%

Rap1b is required for normal platelet function and hemostasis in mice

Smyth²,

et al. 2005

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“…The rap genes, which encode low‐molecular‐weight GTPases are highly conserved among different organisms and have been characterized in a number of diverse species including Dictyostelium (Robbins et al ., 1991), Drosophila (Neuman‐Silberberg et al ., 1984; Hariharan et al ., 1991) and humans (Pizon et al ., 1988; Kitayama et al ., 1989). Rap proteins exhibit ∼50% sequence similarity to Ras proteins at the amino acid level.…”

Section: Introductionmentioning

confidence: 99%

The Rap1 GTPase functions as a regulator of morphogenesis invivo

et al. 1999

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The Ras-related Rap GTPases are highly conserved across diverse species but their normal biological function is not well understood. Initial studies in mammalian cells suggested a role for Rap as a Ras antagonist. More recent experiments indicate functions in calcium-and cAMP-mediated signaling and it has been proposed that protein kinase A-mediated phosphorylation activates Rap in vivo. We show that Ras1-mediated signaling pathways in Drosophila are not influenced by Rap1 levels, suggesting that Ras1 and Rap1 function via distinct pathways. Moreover, a mutation that abolishes the putative cAMP-dependent kinase phosphorylation site of Drosophila Rap1 can still rescue the Rap1 mutant phenotype. Our experiments show that Rap1 is not needed for cell proliferation and cell-fate specification but demonstrate a critical function for Rap1 in regulating normal morphogenesis in the eye disk, the ovary and the embryo. Rap1 mutations also disrupt cell migrations and cause abnormalities in cell shape. These findings indicate a role for Rap proteins as regulators of morphogenesis in vivo.

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“…The increase in transcription of both the repD and E genes is quite early in development, and it will be of interest to see how they interact with the signaling pathways that have been demonstrated to be acting at this time. For example, ras genes are expressed in early Dictyostelium development (48) and ras mediated signaling is involved in the induction of the transcriptional response to UV damage in yeast and mammals (49).…”

Section: Discussionmentioning

confidence: 99%

Differential developmental expression of the repB and repD Xeroderma pigmentosum related DNA helicase genes from Dictyostelium discoideum

Lee

Garcia

et al. 1997

Nucleic Acids Research

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DNA helicases are essential to many cellular processes including recombination, replication and transcription, and some helicases function in multiple processes. The helicases encoded by the Xeroderma pigmentosum (XP) B and D genes function in both nucleotide excision repair and transcription initiation. Mutations that affect the repair function of these proteins result in XP while mutations affecting transcription result in neurological and developmental abnormalities, although the underlying molecular and cellular basis for these phenotypes is not well understood. To better understand the developmental roles of these genes, we have now identified and characterized the rep B and rep D genes from the cellular slime mold Dictyostelium discoideum . Both genes encode DNA helicases of the SF2 superfamily of helicases. The rep D gene contains no introns and the rep B gene contains only one intron, which makes their genomic structures dramatically different from the corresponding genes in mammals and fish. However the predicted Dictyostelium proteins share high homology with the human XPB and XPD proteins. The single copy of the rep B and D genes map to chromosomes 3 and 1, respectively. The expression of rep B and D (and the previously isolated rep E) genes during multicellular development was examined, and it was determined that each rep gene has a unique pattern of expression, consistent with the idea that they have specific roles in development. The pattern and extent of expression of these genes was not affected by the growth history of the cells, implying that the expression of these genes is tightly regulated by the developmental program. The expression of the rep genes is a very early step in development and may well represent a key event in the initiation of development in this organism.

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Ras‐related genes in Dictyostelium discoideum

Cited by 10 publications

References 38 publications

Rap1b is required for normal platelet function and hemostasis in mice

Rap1b is required for normal platelet function and hemostasis in mice

The Rap1 GTPase functions as a regulator of morphogenesis invivo

Differential developmental expression of the repB and repD Xeroderma pigmentosum related DNA helicase genes from Dictyostelium discoideum

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