Solution structure of the human Grb14-SH2 domain and comparison with the structures of the human Grb7-SH2/erbB2 peptide complex and human Grb10-SH2 domain.
Grb14 is an adapter protein that is known to be overexpressed in estrogen receptor positive breast cancers, and in a number of prostate cancer cell lines. Grb14 has been demonstrated to bind to a number of activated receptor tyrosine kinases (RTKs) and to modulate signals transduced through these receptors. The RTKs to which Grb14 binds include the insulin receptor (IR), the fibroblast growth factor receptor (FGFR), the platelet-derived growth factor receptor (PDGFR), and the tunica endothelial kinase (Tek/Tie2) receptor. Grb14 has been shown to bind to these activated RTKs through its Src homology 2 (SH2) domain, with the exception of the insulin receptor, where the primary binding interaction is via a small domain adjacent to the SH2 domain (the BPS or PIR domain). Grb14 is a member of the Grb7 family of proteins, which also includes Grb7 and Grb10. We have solved the solution structure of the human Grb14-SH2 domain and compared it with the recently determined Grb7-SH2 and Grb10-SH2 domain structures.
Scharf
Paul J
PJ
Department of Biochemistry, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA.
Witney
Jill
J
Daly
Roger
R
Lyons
Barbara A
BA
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D051382:GRB7 Adaptor Protein; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry; D019000:Phosphotyrosine / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D012996:Solutions; D040681:Structural Homology, Protein; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051382:GRB7 Adaptor Protein; D046912:Multiprotein Complexes; D019000:Phosphotyrosine; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D012996:Solutions; C099655:GRB14 protein, human; C495955:GRB7 protein, human