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Transmembrane phosphoprotein Cbp senses cell adhesion signaling mediated by Src family kinase in lipid rafts
- Source :
- Proceedings of the National Academy of Sciences. 100:14897-14902
- Publication Year :
- 2003
- Publisher :
- Proceedings of the National Academy of Sciences, 2003.
-
Abstract
- Cbp, a C-terminal Src kinase (Csk)-binding protein, is a transmembrane phosphoprotein that has been implicated in the regulation of the Src family kinase (SFK) through recruiting Csk, a negative regulator of SFK, to a membrane microdomain of lipid rafts. To examine the contribution of Cbp to cell adhesion signaling mediated by SFK, we investigated the kinase responsible for phosphorylating Cbp and the mode of phosphorylation during the cell adhesion process. The results obtained by using mutant mice or cells that lack Csk and/or a member of SFK, Fyn, reveal that Cbp is phosphorylated predominantly by raft-localized Fyn in vivo . Upon cell adhesion onto fibronectin, Cbp becomes transiently phosphorylated (consistent with SFK activation) and recruits Csk to lipid rafts. These events are completed before the full activation of focal adhesion kinase, indicating that the transient activation and down-regulation of SFK in lipid rafts are earlier events in cell adhesion signaling. In Csk-deficient cells, continuous hyperactivation of SFK leads to continuous hyperphosphorylation of Cbp, accompanied by impaired cell spreading and migration. Silencing of Cbp by RNA interference also induced impaired cell spreading. These findings suggest that Cbp could serve as a sensor of SFK activity in early stages of cell adhesion signaling, and that Csk-mediated down-regulation of SFK is essential to allow dynamic cellular events involved in the regulation of cell spreading and migration.
- Subjects :
- Integrins
DNA, Complementary
Time Factors
Integrin
Biology
environment and public health
Culture Media, Serum-Free
Cell membrane
Focal adhesion
Mice
Membrane Microdomains
FYN
Cell Movement
Cell Adhesion
medicine
Animals
Src family kinase
Phosphorylation
Cell adhesion
Cytoskeleton
Multidisciplinary
Cell Membrane
Brain
Membrane Proteins
Biological Sciences
Lipid Metabolism
Phosphoproteins
Fibronectins
Cell biology
Cell Adhesion Process
src-Family Kinases
medicine.anatomical_structure
biology.protein
Tyrosine
RNA Interference
Signal Transduction
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....11e2dfb2bf37b41e3539fb23c5cc0e21