Interactions between the bud emergence proteins Bem1p and Bem2p and Rho-type GTPases in yeast.

Peterson, Julie A.; Zheng, Yi; Bender, Laurel; Myers, Alan M.; Cerione, Richard A.; Bender, Alan

doi:10.1083/jcb.127.5.1395

Cited by 195 publications

(225 citation statements)

References 60 publications

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“…The morphology defects and presence of higher amounts of active (GTP-bound) Rho GTPase and of phosphorylated CgSlt2 in mutants lacking CgBEM2 suggest that CgBem2 functions as a GAP for CgRho1, consistent with its known role in S. cerevisiae (53). The Rho family of GTPases is known to perform myriad functions in diverse cellular processes through different effector molecules partly due to the target specificities, functional diversities, and individual regulation of their GAPs (26,54).…”

Section: Discussionmentioning

confidence: 60%

The Rho1 GTPase-activating Protein CgBem2 Is Required for Survival of Azole Stress in Candida glabrata

Borah¹,

Shivarathri

Kaur

2011

Journal of Biological Chemistry

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Invasive fungal infections are common clinical complications of neonates, critically ill, and immunocompromised patients worldwide. Candida species are the leading cause of disseminated fungal infections, with Candida albicans being the most prevalent species. Candida glabrata, the second/third most common cause of candidemia, shows reduced susceptibility to a widely used antifungal drug fluconazole. Here, we present findings from a screen of 9134 C. glabrata Tn7 insertion mutants for altered survival profiles in the presence of fluconazole. We have identified two components of RNA polymerase II mediator complex, three players of Rho GTPase-mediated signaling cascade, and two proteins implicated in actin cytoskeleton biogenesis and ergosterol biosynthesis that are required to sustain viability during fluconazole stress. We show that exposure to fluconazole leads to activation of the protein kinase C (PKC)-mediated cell wall integrity pathway in C. glabrata. Our data demonstrate that disruption of a RhoGAP (GTPase activating protein) domain-containing protein, CgBem2, results in budemergence defects, azole susceptibility, and constitutive activation of CgRho1-regulated CgPkc1 signaling cascade and cell wall-related phenotypes. The viability loss of Cgbem2⌬ mutant upon fluconazole treatment could be partially rescued by the PKC inhibitor staurosporine. Additionally, we present evidence that CgBEM2 is required for the transcriptional activation of genes encoding multidrug efflux pumps in response to fluconazole exposure. Last, we report that Hsp90 inhibitor geldanamycin renders fluconazole a fungicidal drug in C. glabrata.

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Section: Discussionmentioning

confidence: 60%

The Rho1 GTPase-activating Protein CgBem2 Is Required for Survival of Azole Stress in Candida glabrata

Borah¹,

Shivarathri

Kaur

2011

Journal of Biological Chemistry

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“…We next investigated the effect of abolishing SKM1 activity in mutants affected in the septin-encoding gene CDC10 (Longtine et al, 1996), in the Rho1p-GAP-encoding gene BEM2 (Peterson et al, 1994), and in the Rho-like protein coded by CDC42, by crossing the Y881, 918-8A and DJTD2-16D strains, respectively, to strains carrying the skm1⌬::URA3 mutation. Double-mutant segregants displayed the same morphogenetic defects as the single mutant strains.…”

Section: Skm1p Does Not Interact Genetically With Other Morphogeneticmentioning

confidence: 99%

**Characterization of SKM1, a Saccharomyces cerevisiae gene encoding a novel Ste20/PAK‐like protein kinase**

Martı́n

Mendoza

Rodrı́guez-Pachón

et al. 1997

Molecular Microbiology

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SummarySte20/PAK serine/threonine protein kinases have been suggested as playing essential roles in cell signalling and morphogenesis as potential targets of Cdc42 and Rac GTPases. We have isolated and characterized the Saccharomyces cerevisiae SKM1 gene, which codes for a novel member of this family of protein kinases. The amino acid sequence analysis of Skm1p revealed the presence of a PH domain and a putative p21-binding domain near its amino terminus, suggesting its involvement in cellular signalling or cytoskeletal functions. However, deletion of SKM1 produced no detectable phenotype under standard laboratory conditions. Moreover, disruption of each of the two other S. cerevisiae Ste20/PAK-like kinase-encoding genes, STE20 and CLA4, in skm1 backgrounds, showed that Skm1p is not redundant with Ste20p or Cla4p. Interestingly, overexpression of SKM1 led to morphological alterations, indicating a possible role for this protein in morphogenetic control. Furthermore, overproduction of Skm1p lacking its N-terminus caused growth arrest. This effect was also seen when similarly truncated versions of Ste20p or Cla4p were overexpressed. We further observed that overproduction of this C-terminal fragment of Skm1p complements the mating defect of a ste20 mutant strain. These results suggest that the N-terminal domains of S. cerevisiae Ste20/ PAK-like protein kinases share a negative regulatory function and play a role in substrate specificity.

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“…Cdc24 may form a complex with Rsr1-GTP at the presumptive bud site and may thereby get activated in a Cdc28 kinase-dependent manner (53). The formation of this complex might involve Bem1 (60). Cla2 could therefore be a target for Cln2, whose activation would prevent activation of Rsr1.…”

Section: Activation Of the Pathway Due To A Deletion In Rga1 Is Not Rmentioning

confidence: 99%

Overexpression of the G1-cyclin Gene CLN2Represses the Mating Pathway in Saccharomyces cerevisiaeat the Level of the MEKK Ste11

Wassmann¹,

Ammerer

1997

Journal of Biological Chemistry

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Basal and induced transcription of pheromonedependent genes is regulated in a cell cycle-dependent way. FUS1, a gene strongly induced after pheromone treatment, shows high mRNA levels in mitosis and early G 1 phase of the cell cycle, a decrease in G 1 after START and again an increase in S phase. Overexpression of CLN2 was shown to repress the transcript number of pheromone-dependent genes (1). We asked whether the activities of components of the mating pathway fluctuate during the cell cycle. We were also interested in determining at what level Cln2 represses the signal transduction machinery. Here we show that the activity of the mitogen-activated protein kinase Fus3 indeed fluctuates during the cell cycle, reflecting the oscillations of the gene transcripts. CLN2 overexpression represses Fus3 kinase activity, independently of the phosphatase Msg5. Additionally, we show that the activity of the MEK Ste7 also fluctuates during the cell cycle. Increased Cln2 levels repress the ability of hyperactive STE11 alleles to induce the pathway. G protein-independent activation of Ste11 caused by an rga1 pbs2 mutation is resistant to high levels of Cln2 kinase. Therefore our results suggest that Cln2-dependent repression of the mating pathway occurs at the level of Ste11.

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Interactions between the bud emergence proteins Bem1p and Bem2p and Rho-type GTPases in yeast.

Abstract: Abstract. The SH3 domain-containing protein Bemlp is needed for normal bud emergence and mating projection formation, two processes that require asymmetric reorganizations of the cortical cytoskeleton in Saccharomyces cerevisiae.

Cited by 195 publications

References 60 publications

The Rho1 GTPase-activating Protein CgBem2 Is Required for Survival of Azole Stress in Candida glabrata

The Rho1 GTPase-activating Protein CgBem2 Is Required for Survival of Azole Stress in Candida glabrata

**Characterization of SKM1, a Saccharomyces cerevisiae gene encoding a novel Ste20/PAK‐like protein kinase**

Overexpression of the G1-cyclin Gene CLN2Represses the Mating Pathway in Saccharomyces cerevisiaeat the Level of the MEKK Ste11

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