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Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains Differentially Modulates Src Kinase Activity in Brain Maturation
- Source :
- PLoS ONE; Vol 6, PLoS ONE, Vol 6, Iss 9, p e23978 (2011), PLoS ONE
- Publication Year :
- 2011
- Publisher :
- Public Library of Science, 2011.
-
Abstract
- Src family kinases (SFK) control multiple processes during brain development and function. We show here that the phosphoprotein associated with glycosphigolipid-enriched microdomains (PAG)/Csk binding protein (Cbp) modulates SFK activity in the brain. The timing and localization of PAG expression overlap with Fyn and Src, both of which we find associated to PAG. We demonstrate in newborn (P1) mice that PAG negatively regulates Src family kinases (SFK). P1 Pag1(-/-) mouse brains show decreased recruitment of Csk into lipid rafts, reduced phosphorylation of the inhibitory tyrosines within SFKs, and an increase in SFK activity of >/ = 50%. While in brain of P1 mice, PAG and Csk are highly and ubiquitously expressed, little Csk is found in adult brain suggesting altered modes of SFK regulation. In adult brain Pag1-deficiency has no effect upon Csk-distribution or inhibitory tyrosine phosphorylation, but kinase activity is now reduced (-20-30%), pointing to the development of a compensatory mechanism that may involve PSD93. The distribution of the Csk-homologous kinase CHK is not altered. Importantly, since the activities of Fyn and Src are decreased in adult Pag1(-/-) mice, thus presenting the reversed phenotype of P1, this provides the first in vivo evidence for a Csk-independent positive regulatory function for PAG in the brain.
- Subjects :
- Mouse
lcsh:Medicine
Signal transduction
Biochemistry
Neurological Signaling
Mice
chemistry.chemical_compound
Molecular cell biology
0302 clinical medicine
Signaling in Cellular Processes
lcsh:Science
In Situ Hybridization
Protein kinase signaling cascade
Mice, Knockout
Neurons
0303 health sciences
Multidisciplinary
Tyrosine-protein kinase CSK
TCR signaling cascade
Reverse Transcriptase Polymerase Chain Reaction
Kinase
Mechanisms of Signal Transduction
Brain
Signaling cascades
Animal Models
Signaling in Selected Disciplines
Feeback Regulation
src-Family Kinases
Intercellular Signaling Peptides and Proteins
Phosphorylation
Cellular Types
Transmembrane Signaling
Tyrosine kinase signaling cascade
Research Article
Proto-oncogene tyrosine-protein kinase Src
Blotting, Western
Biology
Immunological Signaling
Protein Chemistry
Signaling Pathways
Glycosphingolipids
03 medical and health sciences
Model Organisms
FYN
Developmental Neuroscience
Animals
Immunoprecipitation
Kinase activity
Protein Interactions
030304 developmental biology
lcsh:R
Membrane Proteins
Proteins
Tyrosine phosphorylation
Signal Termination
Phosphoproteins
Molecular biology
Regulatory Proteins
Transmembrane Proteins
Animals, Newborn
chemistry
nervous system
Cellular Neuroscience
Phosphoprotein
lcsh:Q
Molecular Neuroscience
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 6
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....6d8978b9bcb9128828fc7fd74ae5d178
- Full Text :
- https://doi.org/10.1371/journal.pone.0023978