title: SH3 domain tyrosine phosphorylation--sites, role and evolution.
abstract: 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.
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Tatárová
authors.forename: Jan
authors.initials: J
authors.lastname: Brábek
authors.forename: Daniel
authors.initials: D
authors.lastname: Rösel
authors.forename: Marian
authors.initials: M
authors.lastname: Novotný
mesh_terms: D000595:Amino Acid Sequence; D005075:Biological Evolution; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D014443:Tyrosine