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Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases

Nore, Beston F; Mattsson, Pekka T; Antonsson, Per; Backesjo, Carl-Magnus; Westlund, Anna; Lennartsson, Johan; Hansson, Henrik; Low, Peter; Rönnstrand, Lars LU and Smith, C I Edvard (2003) In Biochimica et Biophysica Acta 1645(2). p.123-132
Abstract
Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the SH3 domain via a transphosphorylation mechanism, which for Bruton's tyrosine kinase (Btk) affects tyrosine 223. We found that TFKs phosphorylate preferentially their own SH3 domains, but differentially phosphorylate other member family SH3 domains, whereas non-related SH3 domains are not phosphorylated. We demonstrate that SH3 domains are good and reliable substrates. We observe that transphosphorylation is selective not only for SH3 domains, but also for dual SH3SH2 domains. However, the dual domain... (More)
Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the SH3 domain via a transphosphorylation mechanism, which for Bruton's tyrosine kinase (Btk) affects tyrosine 223. We found that TFKs phosphorylate preferentially their own SH3 domains, but differentially phosphorylate other member family SH3 domains, whereas non-related SH3 domains are not phosphorylated. We demonstrate that SH3 domains are good and reliable substrates. We observe that transphosphorylation is selective not only for SH3 domains, but also for dual SH3SH2 domains. However, the dual domain is phosphorylated more effectively. The major phosphorylation sites were identified as conserved tyrosines, for Itk Y180 and for Bmx Y215, both sites being homologous to the Y223 site in Btk. There is, however, one exception because the Tec-SH3 domain is phosphorylated at a non-homologous site, nevertheless a conserved tyrosine, Y206. Consistent with these findings, the 3D structures for SH3 domains point out that these phosphorylated tyrosines are located on the ligand-binding surface. Because a number of Tec family kinases are coexpressed in cells, it is possible that they could regulate the activity of each other through transphosphorylation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Immunodeficiency, Tyrosine kinase, Btk, Itk, Tec, Bmx, Signal transduction, X-linked agammaglobulinemia, XLA
in
Biochimica et Biophysica Acta
volume
1645
issue
2
pages
123 - 132
publisher
Elsevier
external identifiers
  • pmid:12573241
  • scopus:10744220325
ISSN
0006-3002
DOI
10.1016/S1570-9639(02)00524-1
language
English
LU publication?
yes
id
b7c6e024-0eb4-48b1-b0c4-f4b39cf3928d (old id 1126219)
date added to LUP
2008-06-12 08:54:38
date last changed
2018-01-07 08:36:06
@article{b7c6e024-0eb4-48b1-b0c4-f4b39cf3928d,
  abstract     = {Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the SH3 domain via a transphosphorylation mechanism, which for Bruton's tyrosine kinase (Btk) affects tyrosine 223. We found that TFKs phosphorylate preferentially their own SH3 domains, but differentially phosphorylate other member family SH3 domains, whereas non-related SH3 domains are not phosphorylated. We demonstrate that SH3 domains are good and reliable substrates. We observe that transphosphorylation is selective not only for SH3 domains, but also for dual SH3SH2 domains. However, the dual domain is phosphorylated more effectively. The major phosphorylation sites were identified as conserved tyrosines, for Itk Y180 and for Bmx Y215, both sites being homologous to the Y223 site in Btk. There is, however, one exception because the Tec-SH3 domain is phosphorylated at a non-homologous site, nevertheless a conserved tyrosine, Y206. Consistent with these findings, the 3D structures for SH3 domains point out that these phosphorylated tyrosines are located on the ligand-binding surface. Because a number of Tec family kinases are coexpressed in cells, it is possible that they could regulate the activity of each other through transphosphorylation.},
  author       = {Nore, Beston F and Mattsson, Pekka T and Antonsson, Per and Backesjo, Carl-Magnus and Westlund, Anna and Lennartsson, Johan and Hansson, Henrik and Low, Peter and Rönnstrand, Lars and Smith, C I Edvard},
  issn         = {0006-3002},
  keyword      = {Immunodeficiency,Tyrosine kinase,Btk,Itk,Tec,Bmx,Signal transduction,X-linked agammaglobulinemia,XLA},
  language     = {eng},
  number       = {2},
  pages        = {123--132},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta},
  title        = {Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases},
  url          = {http://dx.doi.org/10.1016/S1570-9639(02)00524-1},
  volume       = {1645},
  year         = {2003},
}