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SH3 Domain Tyrosine Phosphorylation – Sites, Role and Evolution

BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESU...

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Autores principales: Tatárová, Zuzana, Brábek, Jan, Rösel, Daniel, Novotný, Marian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352900/
https://www.ncbi.nlm.nih.gov/pubmed/22615764
http://dx.doi.org/10.1371/journal.pone.0036310
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author Tatárová, Zuzana
Brábek, Jan
Rösel, Daniel
Novotný, Marian
author_facet Tatárová, Zuzana
Brábek, Jan
Rösel, Daniel
Novotný, Marian
author_sort Tatárová, Zuzana
collection PubMed
description BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESULTS: To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c–Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F). This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains. Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions. The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners.
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spelling pubmed-33529002012-05-21 SH3 Domain Tyrosine Phosphorylation – Sites, Role and Evolution Tatárová, Zuzana Brábek, Jan Rösel, Daniel Novotný, Marian PLoS One Research Article BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESULTS: To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c–Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F). This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains. Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions. The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners. Public Library of Science 2012-05-15 /pmc/articles/PMC3352900/ /pubmed/22615764 http://dx.doi.org/10.1371/journal.pone.0036310 Text en Tatárová et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tatárová, Zuzana
Brábek, Jan
Rösel, Daniel
Novotný, Marian
SH3 Domain Tyrosine Phosphorylation – Sites, Role and Evolution
title SH3 Domain Tyrosine Phosphorylation – Sites, Role and Evolution
title_full SH3 Domain Tyrosine Phosphorylation – Sites, Role and Evolution
title_fullStr SH3 Domain Tyrosine Phosphorylation – Sites, Role and Evolution
title_full_unstemmed SH3 Domain Tyrosine Phosphorylation – Sites, Role and Evolution
title_short SH3 Domain Tyrosine Phosphorylation – Sites, Role and Evolution
title_sort sh3 domain tyrosine phosphorylation – sites, role and evolution
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352900/
https://www.ncbi.nlm.nih.gov/pubmed/22615764
http://dx.doi.org/10.1371/journal.pone.0036310
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