Direct binding of Shc, Grb2, SHP-2 and p40 to the murine granulocyte colony-stimulating factor receptor.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Animals, Bone Marrow Cells, Cells, Cultured, DNA-Binding Proteins, GRB2 Adaptor Protein, Intracellular Signaling Peptides and Proteins, Mice, NADPH Oxidase, Phosphorylation, Protein Binding, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Proteins, Receptor, Epidermal Growth Factor, Receptors, Granulocyte Colony-Stimulating Factor, Recombinant Proteins, SH2 Domain-Containing Protein Tyrosine Phosphatases, Shc Signaling Adaptor Proteins, Signal Transduction, src Homology Domains
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Animals, Bone Marrow Cells, Cells, Cultured, DNA-Binding Proteins, GRB2 Adaptor Protein, Intracellular Signaling Peptides and Proteins, Mice, NADPH Oxidase, Phosphorylation, Protein Binding, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Proteins, Receptor, Epidermal Growth Factor, Receptors, Granulocyte Colony-Stimulating Factor, Recombinant Proteins, SH2 Domain-Containing Protein Tyrosine Phosphatases, Shc Signaling Adaptor Proteins, Signal Transduction, src Homology Domains
Biochim. Biophys. Acta
Date: Nov. 19, 1998
PubMed ID: 9824671
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