Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1126219
- author
- 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
- organization
- publishing date
- 2003
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- b7c6e024-0eb4-48b1-b0c4-f4b39cf3928d (old id 1126219)
- date added to LUP
- 2016-04-01 15:24:04
- date last changed
- 2022-01-28 05:10:39
@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}}, keywords = {{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}}, doi = {{10.1016/S1570-9639(02)00524-1}}, volume = {{1645}}, year = {{2003}}, }