β3-Chimaerin, a novel member of the chimaerin Rac-GAP family

Chimaerins are a family of diacylglycerol- and phorbol ester-regulated GTPase activating proteins (GAPs) for the small G-protein Rac. Extensive evidence indicates that these proteins play important roles in development, axon guidance, metabolism, cell motility, and T cell activation. Four isoforms h...

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Autores principales: Zubeldia-Brenner, L., Gutierrez-Uzquiza, A., Barrio-Real, L., Wang, H., Kazanietz, M.G., Leskow, F.C.
Formato: JOUR
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_03014851_v41_n4_p2067_ZubeldiaBrenner
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spelling todo:paper_03014851_v41_n4_p2067_ZubeldiaBrenner2023-10-03T15:18:28Z β3-Chimaerin, a novel member of the chimaerin Rac-GAP family Zubeldia-Brenner, L. Gutierrez-Uzquiza, A. Barrio-Real, L. Wang, H. Kazanietz, M.G. Leskow, F.C. C1 domain Chimaerin CHN2 Phorbol esters Rac-GAP alpha1 chimaerin alpha2 chimaerin beta1 chimaerin beta2 chimaerin beta3 chimaerin chimerin guanosine triphosphatase activating protein isoprotein phorbol ester unclassified drug chimaerin-beta3 protein, human chimerin isoprotein phorbol 13 acetate 12 myristate protein binding Rac protein alternative RNA splicing amino terminal sequence article bioinformatics CHN1 gene CHN2 gene controlled study enzyme activity enzyme analysis epididymis exon genetic analysis human human cell human tissue leukocyte nucleotide sequence promoter region protein analysis protein domain protein expression spleen thymus tissue distribution transcription initiation site amino acid sequence animal antibody specificity cell line chemistry Chlorocebus aethiops COS 1 cell line drug effects enzyme activation gene expression gene expression profiling gene expression regulation gene order genetics metabolism molecular genetics Alternative Splicing Amino Acid Sequence Animals Base Sequence Cell Line Cercopithecus aethiops Chimerin Proteins COS Cells Enzyme Activation Gene Expression Gene Expression Profiling Gene Expression Regulation Gene Order Humans Molecular Sequence Data Organ Specificity Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Protein Isoforms rac GTP-Binding Proteins Tetradecanoylphorbol Acetate Chimaerins are a family of diacylglycerol- and phorbol ester-regulated GTPase activating proteins (GAPs) for the small G-protein Rac. Extensive evidence indicates that these proteins play important roles in development, axon guidance, metabolism, cell motility, and T cell activation. Four isoforms have been reported to-date, which are products of CHN1 (α1- and α2-chimaerins) and CHN2 (β1- and β2-chimaerins) genes. Although these gene products are assumed to be generated by alternative splicing, bioinformatics analysis of the CHN2 gene revealed that β1- and β2-chimaerins are the products of alternative transcription start sites (TSSs) in different promoter regions. Furthermore, we found an additional TSS in CHN2 gene that leads to a novel product, which we named β3-chimaerin. Expression profile analysis revealed predominantly low levels for the β3-chimaerin transcript, with higher expression levels in epididymis, plasma blood leucocytes, spleen, thymus, as well as various areas of the brain. In addition to the prototypical SH2, C1, and Rac-GAP domains, β3-chimaerin has a unique N-terminal domain. Studies in cells established that β3-chimaerin has Rac-GAP activity and is responsive to phorbol esters. The enhanced responsiveness of β3-chimaerin for phorbol ester-induced translocation relative to β2-chimaerin suggests differential ligand accessibility to the C1 domain. © 2014 Springer Science+Business Media Dordrecht. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03014851_v41_n4_p2067_ZubeldiaBrenner
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic C1 domain
Chimaerin
CHN2
Phorbol esters
Rac-GAP
alpha1 chimaerin
alpha2 chimaerin
beta1 chimaerin
beta2 chimaerin
beta3 chimaerin
chimerin
guanosine triphosphatase activating protein
isoprotein
phorbol ester
unclassified drug
chimaerin-beta3 protein, human
chimerin
isoprotein
phorbol 13 acetate 12 myristate
protein binding
Rac protein
alternative RNA splicing
amino terminal sequence
article
bioinformatics
CHN1 gene
CHN2 gene
controlled study
enzyme activity
enzyme analysis
epididymis
exon
genetic analysis
human
human cell
human tissue
leukocyte
nucleotide sequence
promoter region
protein analysis
protein domain
protein expression
spleen
thymus
tissue distribution
transcription initiation site
amino acid sequence
animal
antibody specificity
cell line
chemistry
Chlorocebus aethiops
COS 1 cell line
drug effects
enzyme activation
gene expression
gene expression profiling
gene expression regulation
gene order
genetics
metabolism
molecular genetics
Alternative Splicing
Amino Acid Sequence
Animals
Base Sequence
Cell Line
Cercopithecus aethiops
Chimerin Proteins
COS Cells
Enzyme Activation
Gene Expression
Gene Expression Profiling
Gene Expression Regulation
Gene Order
Humans
Molecular Sequence Data
Organ Specificity
Promoter Regions, Genetic
Protein Binding
Protein Interaction Domains and Motifs
Protein Isoforms
rac GTP-Binding Proteins
Tetradecanoylphorbol Acetate
spellingShingle C1 domain
Chimaerin
CHN2
Phorbol esters
Rac-GAP
alpha1 chimaerin
alpha2 chimaerin
beta1 chimaerin
beta2 chimaerin
beta3 chimaerin
chimerin
guanosine triphosphatase activating protein
isoprotein
phorbol ester
unclassified drug
chimaerin-beta3 protein, human
chimerin
isoprotein
phorbol 13 acetate 12 myristate
protein binding
Rac protein
alternative RNA splicing
amino terminal sequence
article
bioinformatics
CHN1 gene
CHN2 gene
controlled study
enzyme activity
enzyme analysis
epididymis
exon
genetic analysis
human
human cell
human tissue
leukocyte
nucleotide sequence
promoter region
protein analysis
protein domain
protein expression
spleen
thymus
tissue distribution
transcription initiation site
amino acid sequence
animal
antibody specificity
cell line
chemistry
Chlorocebus aethiops
COS 1 cell line
drug effects
enzyme activation
gene expression
gene expression profiling
gene expression regulation
gene order
genetics
metabolism
molecular genetics
Alternative Splicing
Amino Acid Sequence
Animals
Base Sequence
Cell Line
Cercopithecus aethiops
Chimerin Proteins
COS Cells
Enzyme Activation
Gene Expression
Gene Expression Profiling
Gene Expression Regulation
Gene Order
Humans
Molecular Sequence Data
Organ Specificity
Promoter Regions, Genetic
Protein Binding
Protein Interaction Domains and Motifs
Protein Isoforms
rac GTP-Binding Proteins
Tetradecanoylphorbol Acetate
Zubeldia-Brenner, L.
Gutierrez-Uzquiza, A.
Barrio-Real, L.
Wang, H.
Kazanietz, M.G.
Leskow, F.C.
β3-Chimaerin, a novel member of the chimaerin Rac-GAP family
topic_facet C1 domain
Chimaerin
CHN2
Phorbol esters
Rac-GAP
alpha1 chimaerin
alpha2 chimaerin
beta1 chimaerin
beta2 chimaerin
beta3 chimaerin
chimerin
guanosine triphosphatase activating protein
isoprotein
phorbol ester
unclassified drug
chimaerin-beta3 protein, human
chimerin
isoprotein
phorbol 13 acetate 12 myristate
protein binding
Rac protein
alternative RNA splicing
amino terminal sequence
article
bioinformatics
CHN1 gene
CHN2 gene
controlled study
enzyme activity
enzyme analysis
epididymis
exon
genetic analysis
human
human cell
human tissue
leukocyte
nucleotide sequence
promoter region
protein analysis
protein domain
protein expression
spleen
thymus
tissue distribution
transcription initiation site
amino acid sequence
animal
antibody specificity
cell line
chemistry
Chlorocebus aethiops
COS 1 cell line
drug effects
enzyme activation
gene expression
gene expression profiling
gene expression regulation
gene order
genetics
metabolism
molecular genetics
Alternative Splicing
Amino Acid Sequence
Animals
Base Sequence
Cell Line
Cercopithecus aethiops
Chimerin Proteins
COS Cells
Enzyme Activation
Gene Expression
Gene Expression Profiling
Gene Expression Regulation
Gene Order
Humans
Molecular Sequence Data
Organ Specificity
Promoter Regions, Genetic
Protein Binding
Protein Interaction Domains and Motifs
Protein Isoforms
rac GTP-Binding Proteins
Tetradecanoylphorbol Acetate
description Chimaerins are a family of diacylglycerol- and phorbol ester-regulated GTPase activating proteins (GAPs) for the small G-protein Rac. Extensive evidence indicates that these proteins play important roles in development, axon guidance, metabolism, cell motility, and T cell activation. Four isoforms have been reported to-date, which are products of CHN1 (α1- and α2-chimaerins) and CHN2 (β1- and β2-chimaerins) genes. Although these gene products are assumed to be generated by alternative splicing, bioinformatics analysis of the CHN2 gene revealed that β1- and β2-chimaerins are the products of alternative transcription start sites (TSSs) in different promoter regions. Furthermore, we found an additional TSS in CHN2 gene that leads to a novel product, which we named β3-chimaerin. Expression profile analysis revealed predominantly low levels for the β3-chimaerin transcript, with higher expression levels in epididymis, plasma blood leucocytes, spleen, thymus, as well as various areas of the brain. In addition to the prototypical SH2, C1, and Rac-GAP domains, β3-chimaerin has a unique N-terminal domain. Studies in cells established that β3-chimaerin has Rac-GAP activity and is responsive to phorbol esters. The enhanced responsiveness of β3-chimaerin for phorbol ester-induced translocation relative to β2-chimaerin suggests differential ligand accessibility to the C1 domain. © 2014 Springer Science+Business Media Dordrecht.
format JOUR
author Zubeldia-Brenner, L.
Gutierrez-Uzquiza, A.
Barrio-Real, L.
Wang, H.
Kazanietz, M.G.
Leskow, F.C.
author_facet Zubeldia-Brenner, L.
Gutierrez-Uzquiza, A.
Barrio-Real, L.
Wang, H.
Kazanietz, M.G.
Leskow, F.C.
author_sort Zubeldia-Brenner, L.
title β3-Chimaerin, a novel member of the chimaerin Rac-GAP family
title_short β3-Chimaerin, a novel member of the chimaerin Rac-GAP family
title_full β3-Chimaerin, a novel member of the chimaerin Rac-GAP family
title_fullStr β3-Chimaerin, a novel member of the chimaerin Rac-GAP family
title_full_unstemmed β3-Chimaerin, a novel member of the chimaerin Rac-GAP family
title_sort β3-chimaerin, a novel member of the chimaerin rac-gap family
url http://hdl.handle.net/20.500.12110/paper_03014851_v41_n4_p2067_ZubeldiaBrenner
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