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The Src-like adaptor protein regulates PDGF-induced actin dorsal ruffles in a c-Cbl-dependent manner
- Source :
- Oncogene, Oncogene, Nature Publishing Group, 2008, 27 (24), pp.3494-500. ⟨10.1038/sj.onc.1211011⟩
- Publication Year :
- 2008
- Publisher :
- HAL CCSD, 2008.
-
Abstract
- The Src-like adaptor protein (SLAP) belongs to the subfamily of adapter proteins that negatively regulate cellular signalling initiated by tyrosine kinases. SLAP has a unique, myristylated N-terminus, followed by SH3 and SH2 domains with high homology to Src family tyrosine kinases (SFK) and a unique C-terminal tail, which is important for c-Cbl binding. We have previously shown that SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and we now report that it regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodelling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signalling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signalling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signalling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl.
- Subjects :
- MESH: Signal Transduction
Cancer Research
MESH: rac GTP-Binding Proteins
SRC Family Tyrosine Kinase
SH2 domain
environment and public health
Mice
Receptors, Platelet-Derived Growth Factor
MESH: Animals
MESH: Proto-Oncogene Proteins c-cbl
MESH: Receptors, Platelet-Derived Growth Factor
Proto-Oncogene Proteins c-cbl
Phosphorylation
STAT3
Lung
Platelet-Derived Growth Factor
0303 health sciences
biology
030302 biochemistry & molecular biology
MESH: Platelet-Derived Growth Factor
Signal transducing adaptor protein
Cell biology
rac GTP-Binding Proteins
src-Family Kinases
Tyrosine kinase
Platelet-derived growth factor receptor
Proto-oncogene tyrosine-protein kinase Src
Signal Transduction
Proto-Oncogene Proteins pp60(c-src)
Mitosis
MESH: Binding, Competitive
macromolecular substances
MESH: Actins
Binding, Competitive
03 medical and health sciences
Genetics
Animals
Point Mutation
MESH: Lung
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Molecular Biology
MESH: Mice
030304 developmental biology
MESH: Point Mutation
MESH: Phosphorylation
MESH: Proto-Oncogene Proteins pp60(c-src)
Fibroblasts
MESH: Mitosis
Actins
enzymes and coenzymes (carbohydrates)
MESH: src-Family Kinases
MESH: Fibroblasts
Cancer research
biology.protein
NIH 3T3 Cells
MESH: NIH 3T3 Cells
Subjects
Details
- Language :
- English
- ISSN :
- 09509232 and 14765594
- Database :
- OpenAIRE
- Journal :
- Oncogene, Oncogene, Nature Publishing Group, 2008, 27 (24), pp.3494-500. ⟨10.1038/sj.onc.1211011⟩
- Accession number :
- edsair.doi.dedup.....0817ab5a7a7aa63c85e4de734e5e527b