Cloning and characterization of the S. pombe gene efc25+, a new putative guanine nucleotide exchange factor

Tratner, Isabelle; Fourticq-Esqueöute, Aude; Tillit, Jeanne; Baldacci, Giuseppe

doi:10.1016/s0378-1119(97)00115-7

Cited by 18 publications

(16 citation statements)

References 33 publications

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“…Strains EFC25U (efc25::ura4) and EFC25L (efc25::LEU2) were created by transforming strain SP870 with a BamHI-SacI fragment from pBSEFC25::ura4 and pBSEFC25::LEU2, respectively. The resulting efc25⌬ cells are phenotypically indistinguishable from the efc25⌬ strains as described before (30). A tea1⌬ strain, TEA1U (tea1::ura4), was created using plasmid pSISTea1⌬ as described (20).…”

Section: Methodsmentioning

confidence: 99%

“…The N terminus of Efc25 is not homologous to any known proteins. Although a detailed study of Efc25 had not been carried out, the phenotype of efc25⌬ cells has been reported, round but fertile (30). These interesting observations collectively suggest that Efc25 may specifically regulate the Ras1-Scd1 pathway and that GEFs can play a very important role in establishing specificity for Ras signaling.…”

mentioning

confidence: 99%

“…A gene encoding a second potential Ras1 GEF, efc25 (term derived from "exchange factor cdc25-like"), was isolated unexpectedly in a study intended to isolate the gene encoding a subunit of the DNA polymerase (30). The Efc25 protein contains a C-terminal Cdc25-like catalytic domain, which shares over 30% identity in amino acid sequence with other Ras GEFs.…”

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confidence: 99%

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Two Ras Pathways in Fission Yeast Are Differentially Regulated by Two Ras Guanine Nucleotide Exchange Factors

Papadaki

Pizon

Onken

et al. 2002

Molecular and Cellular Biology

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How a given Ras prreotein coordinates multiple signaling inputs and outputs is a fundamental issue of signaling specificity. Schizosaccharomyces pombe contains one Ras, Ras1, that has two distinct outputs. Ras1 activates Scd1, a presumptive guanine nucleotide exchange factor (GEF) for Cdc42, to control morphogenesis and chromosome segregation, and Byr2, a component of a mitogen-activated protein kinase cascade, to control mating. So far there is only one established Ras1 GEF, Ste6. Paradoxically, ste6 null (ste6⌬) mutants are sterile but normal in cell morphology. This suggests that Ste6 specifically activates the Ras1-Byr2 pathway and that there is another GEF capable of activating the Scd1 pathway. We thereby characterized a potential GEF, Efc25. Genetic data place Efc25 upstream of the Ras1-Scd1, but not the Ras1-Byr2, pathway. Like ras1⌬ and scd1⌬, efc25⌬ is synthetically lethal with a deletion in tea1, a critical element for cell polarity control. Using truncated proteins, we showed that the C-terminal GEF domain of Efc25 is essential for function and regulated by the N terminus. We conclude that Efc25 acts as a Ras1 GEF specific for the Scd1 pathway. While ste6 expression is induced during mating, efc25 expression is constitutive. Moreover, Efc25 overexpression renders cells hyperelongated and sterile; the latter can be rescued by activated Ras1. This suggests that Efc25 can recruit Ras1 to selectively activate Scd1 at the expense of Byr2. Reciprocally, Ste6 overexpression can block Scd1 activation. We propose that external signals can partly segregate two Ras1 pathways by modulating GEF expression and that GEFs can influence how Ras is coupled to specific effectors.Ras G proteins act as molecular switches for signal transduction pathways that are important for cell proliferation, differentiation, cell death, and organization of the cytoskeleton (reviewed in reference 29). In humans, there are three RAS genes (H-, K-, and N-RAS) which encode four Ras proteins with more than 90% identity in amino acid sequence. The biochemical properties of these Ras proteins are very similar and straightforward. Ras can bind either GTP or GDP. In the resting state of the cell, Ras is primarily GDP bound and inactive. In response to signals, Ras switches to the active GTP-bound state, a process catalyzed by guanine nucleotide exchange factors (GEFs). Activated Ras stimulates effector proteins to turn on downstream pathways. How a given Ras protein functions in the cell, however, is anything but straightforward. By one count, there are at least three Ras effectors (Raf, phosphatidylinositol 3-kinase, and Ral GDS; reviewed in reference 29) and three families of GEFs containing at least five members (Sos1, Sos2, GRF1/Cdc25Mm, GRF2, and GRP [2]). Under in vitro conditions, most known Ras effectors and GEFs can frequently interact with more than one Ras protein, but how they actually match up with one another in the cell is poorly understood.We use the fission yeast Schizosaccharomyces pombe as a genetic model organism to study ...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Two Ras Pathways in Fission Yeast Are Differentially Regulated by Two Ras Guanine Nucleotide Exchange Factors

Papadaki

Pizon

Onken

et al. 2002

Molecular and Cellular Biology

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“…Two Cdc25-like exchange factors for Ras1 have been identified as Ste6 and Efc25 (14)(15)(16). Interestingly, they are not functionally interchangeable.…”

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confidence: 99%

Compartmentalized signaling of Ras in fission yeast

Onken

Wiener

Philips

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

119

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Compartment-specific Ras signaling is an emerging paradigm that may explain the multiplex outputs from a single GTPase. The fission yeast, Schizosaccharomyces pombe, affords a simple system in which to study Ras signaling because it has a single Ras protein, Ras1, that regulates two distinct pathways: one that controls mating through a Byr2-mitogen-activated protein kinase cascade and one that signals through Scd1-Cdc42 to maintain elongated cell morphology. We generated Ras1 mutants that are restricted to either the endomembrane or the plasma membrane. Protein binding studies showed that each could interact with the effectors of both pathways. However, when examined in ras1 null cells, endomembrane-restricted Ras1 supported morphology but not mating, and, conversely, plasma membrane-restricted Ras1 supported mating but did not signal to Scd1-Cdc42. These observations provide a striking demonstration of compartment-specific Ras signaling and indicate that spatial specificity in the Ras pathway is evolutionarily conserved.cancer ͉ Cdc42 ͉ Int6 ͉ mitogen-activated protein kinase ͉ eIF3

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“…In this study, we identified sql2 as a multicopy suppressor of the glossy colony phenotype of a gpa3 Q206L strain, which is (34,62). As in S. pombe, the CDC25 homologue of C. albicans is not essential for growth but is needed for the dimorphic switch in response to serum (24).…”

Section: Discussionmentioning

confidence: 99%

Guanyl Nucleotide Exchange Factor Sql2 and Ras2 Regulate Filamentous Growth in Ustilago maydis

et al. 2003

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The cyclic AMP (cAMP)-signaling pathway regulates cell morphology and plays a crucial role during pathogenic development of the plant-pathogenic fungus Ustilago maydis. Strains lacking components of this signaling pathway, such as the G␣-subunit Gpa3 or the adenylyl cyclase Uac1, are nonpathogenic and grow filamentously. On the other hand, strains exhibiting an activated cAMP pathway due to a dominant-active allele of gpa3 display a glossy colony phenotype and are unable to proliferate in plant tumors. Here we present the identification of sql2 as a suppressor of the glossy colony phenotype of a gpa3 Q206L strain. sql2 encodes a protein with similarity to CDC25-like guanine nucleotide exchange factors, which are known to act on Ras proteins. Overexpression of sql2 leads to filamentous growth that cannot be suppressed by exogenous cAMP, suggesting that Sql2 does not act upstream of Uac1. To gain more insight in signaling processes regulated by Sql2, we isolated two genes encoding Ras proteins. Expression of dominant active alleles of ras1 and ras2 showed that Ras2 induces filamentous growth while Ras1 does not affect cell morphology but elevates pheromone gene expression. These results indicate that Ras1 and Ras2 fulfill different functions in U. maydis. Moreover, observed similarities between the filaments induced by sql2 and ras2 suggest that Sql2 is an activator of Ras2. Interestingly, sql2 deletion mutants are affected in pathogenic development but not in mating, indicating a specific function of sql2 during pathogenesis.

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Cloning and characterization of the S. pombe gene efc25+, a new putative guanine nucleotide exchange factor

Cited by 18 publications

References 33 publications

Two Ras Pathways in Fission Yeast Are Differentially Regulated by Two Ras Guanine Nucleotide Exchange Factors

Two Ras Pathways in Fission Yeast Are Differentially Regulated by Two Ras Guanine Nucleotide Exchange Factors

Compartmentalized signaling of Ras in fission yeast

Guanyl Nucleotide Exchange Factor Sql2 and Ras2 Regulate Filamentous Growth in Ustilago maydis

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