Direct binding of Shc, Grb2, SHP-2 and p40 to the murine granulocyte colony-stimulating factor receptor
journal contributionposted on 1998-11-19, 00:00 authored by Alister WardAlister Ward, J L Monkhouse, J A Hamilton, X F Csar
Granulocyte colony-stimulating factor (G-CSF) mediates the proliferation, differentiation and activation of cells in the granulocytic lineage. However, knowledge about the specific signaling pathways utilized by the G-CSF receptor (G-CSF-R) upon ligand binding remains limited. In this report, we show rapid phosphorylation of Shc upon stimulation of NFS-60 cells with G-CSF, and inducible association of Shc and Grb2 with the G-CSF-R in these cells. Using a tyrosine-phosphorylated GST-G-CSF-R fusion we demonstrate that Shc, Grb2 and SHP-2 directly bind the receptor via their respective SH2 domains, suggesting multiple routes of MAPK activation from the G-CSF-R are possible. In addition, we have identified an unknown p40 molecule which is associated with the G-CSF-R transiently following G-CSF stimulation, and a constitutively-associated p37 molecule.
JournalBiochimica et biophysica acta
Pagination70 - 76
LocationAmsterdam, The Netherlands
Link to full text
Publication classificationC1.1 Refereed article in a scholarly journal
Copyright notice1998, Elsevier Science B.V.
Adaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAnimalsBone Marrow CellsCells, CulturedDNA-Binding ProteinsGRB2 Adaptor ProteinIntracellular Signaling Peptides and ProteinsMiceNADPH OxidasePhosphorylationProtein BindingProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesProteinsReceptor, Epidermal Growth FactorReceptors, Granulocyte Colony-Stimulating FactorRecombinant ProteinsSH2 Domain-Containing Protein Tyrosine PhosphatasesShc Signaling Adaptor ProteinsSignal TransductionSrc Homology 2 Domain-Containing, Transforming Protein 1src Homology DomainsGranulocyte colony-stimulating factorGrb2ShcSHP-2Tyrosine phosphorylationSH2 domainScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyCell BiologyPROTEIN-TYROSINE KINASESSIGNAL-TRANSDUCTIONG-CSFRAPID ACTIVATIONNFS-60 CELLSSTAT3PURIFICATIONEXPRESSIONCOMPLEXESRESPONSES