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Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling

Mutations affecting the Schizosaccharomyces pombe cAMP phosphodiesterase (PDE) gene cgs2(+) were identified in a screen for suppressors of mutant alleles of the adenylate cyclase gene (git2(+)/cyr1(+)), which encode catalytically active forms of the enzyme that cannot be stimulated by extracellular...

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Main Authors: Wang, Lili, Griffiths, Kenneth, Zhang, Y. Hi, Ivey, F. Douglas, Hoffman, Charles S.
Formato: Artigo
Idioma:English
Publicado em: Copyright © 2005 by the Genetics Society of America 2005
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Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC1456081/
https://ncbi.nlm.nih.gov/pubmed/16143612
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1534/genetics.105.047233
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spelling pubmed-14560812006-09-13 Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling Wang, Lili Griffiths, Kenneth Zhang, Y. Hi Ivey, F. Douglas Hoffman, Charles S. Genetics Investigations Mutations affecting the Schizosaccharomyces pombe cAMP phosphodiesterase (PDE) gene cgs2(+) were identified in a screen for suppressors of mutant alleles of the adenylate cyclase gene (git2(+)/cyr1(+)), which encode catalytically active forms of the enzyme that cannot be stimulated by extracellular glucose signaling. These mutations suppress both the git2(−) mutant alleles used in the suppressor selection and mutations in git1(+), git3(+), git5(+), git7(+), git10(+), and git11(+), which are all required for adenylate cyclase activation. Notably, these cgs2 mutant alleles fail to suppress mutations in gpa2(+), which encodes the Gα subunit of a heterotrimeric G protein required for adenylate cyclase activation, although the previously identified cgs2-2 allele does suppress loss of gpa2(+). Further analysis of the cgs2-s1 allele reveals a synthetic interaction with the gpa2(R176H)-activated allele, with respect to derepression of fbp1-lacZ transcription in glucose-starved cells. In addition, direct measurements of cAMP levels show that cgs2-s1 cells maintain normal basal cAMP levels, but are severely defective in feedback regulation upon glucose detection. These results suggest that PDE activity in S. pombe may be coordinately regulated with adenylate cyclase activity as part of the feedback regulation mechanism to limit the cAMP response to glucose detection. Copyright © 2005 by the Genetics Society of America 2005-12 /pmc/articles/PMC1456081/ /pubmed/16143612 http://dx.doi.org/10.1534/genetics.105.047233 Text en Copyright © 2005 by the Genetics Society of America
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Investigations
spellingShingle Investigations
Wang, Lili
Griffiths, Kenneth
Zhang, Y. Hi
Ivey, F. Douglas
Hoffman, Charles S.
Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling
description Mutations affecting the Schizosaccharomyces pombe cAMP phosphodiesterase (PDE) gene cgs2(+) were identified in a screen for suppressors of mutant alleles of the adenylate cyclase gene (git2(+)/cyr1(+)), which encode catalytically active forms of the enzyme that cannot be stimulated by extracellular glucose signaling. These mutations suppress both the git2(−) mutant alleles used in the suppressor selection and mutations in git1(+), git3(+), git5(+), git7(+), git10(+), and git11(+), which are all required for adenylate cyclase activation. Notably, these cgs2 mutant alleles fail to suppress mutations in gpa2(+), which encodes the Gα subunit of a heterotrimeric G protein required for adenylate cyclase activation, although the previously identified cgs2-2 allele does suppress loss of gpa2(+). Further analysis of the cgs2-s1 allele reveals a synthetic interaction with the gpa2(R176H)-activated allele, with respect to derepression of fbp1-lacZ transcription in glucose-starved cells. In addition, direct measurements of cAMP levels show that cgs2-s1 cells maintain normal basal cAMP levels, but are severely defective in feedback regulation upon glucose detection. These results suggest that PDE activity in S. pombe may be coordinately regulated with adenylate cyclase activity as part of the feedback regulation mechanism to limit the cAMP response to glucose detection.
author Wang, Lili
Griffiths, Kenneth
Zhang, Y. Hi
Ivey, F. Douglas
Hoffman, Charles S.
author_facet Wang, Lili
Griffiths, Kenneth
Zhang, Y. Hi
Ivey, F. Douglas
Hoffman, Charles S.
author_sort Wang, Lili
title Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling
title_short Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling
title_full Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling
title_fullStr Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling
title_full_unstemmed Schizosaccharomyces pombe Adenylate Cyclase Suppressor Mutations Suggest a Role for cAMP Phosphodiesterase Regulation in Feedback Control of Glucose/cAMP Signaling
title_sort schizosaccharomyces pombe adenylate cyclase suppressor mutations suggest a role for camp phosphodiesterase regulation in feedback control of glucose/camp signaling
publisher Copyright © 2005 by the Genetics Society of America
publisher_facet Copyright © 2005 by the Genetics Society of America
publishDate 2005
url https://ncbi.nlm.nih.gov/pmc/articles/PMC1456081/
https://ncbi.nlm.nih.gov/pubmed/16143612
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1534/genetics.105.047233
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