title: Direct binding of Shc, Grb2, SHP-2 and p40 to the murine granulocyte colony-stimulating factor receptor.
abstract: 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.
authors.affiliation: Institute of Hematology, Room Ee 1330e, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. ward@hema.fgg.eur.nl
authors.forename: A C
authors.initials: AC
authors.lastname: Ward
authors.forename: J L
authors.initials: JL
authors.lastname: Monkhouse
authors.forename: J A
authors.initials: JA
authors.lastname: Hamilton
authors.forename: X F
authors.initials: XF
authors.lastname: Csar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D066246:ErbB Receptors; D051380:GRB2 Adaptor Protein; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D019255:NADPH Oxidases; D010766:Phosphorylation; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019255:NADPH Oxidases; C113333:NCF4 protein, human; D066246:ErbB Receptors; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases