Murine epidermal growth factor peptide (33-42) binds to a YIGSR-specific laminin receptor on both tumor and endothelial cells.
A laminin-antagonist peptide, comprising amino acids 33-42 of murine epidermal growth factor (mEGF-(33-42)), interacts with a breast cancer- and endothelial cell-associated receptor, which is specific for the laminin B1 chain sequence, CDPGYIGSR-NH2 (Lam.B1-(925-933)), and is immunologically similar to a previously described 67-kDa laminin receptor. In whole cell receptor assays, mEGF-(33-42), Lam. B1-(925-933), and laminin all have IC50 values for displacement of 125I-laminin in the range 1-5 nM. Cell attachment to solid-phase laminin is also blocked by all three ligands, but in contrast to the receptor assays, mEGF-(33-42) or Lam.B1-(925-933), while equipotent with each other, were less effective than laminin. The concentrations of the peptides required to produce half-maximal inhibition of attachment were in the range 230-390 nM, but those for laminin were 1000-fold lower, in the range 0.2-0.3 nM. Like laminin, solid-phase mEGF-(33-42) supports cell attachment, and this ability is blocked by anti-67-kDa receptor antibodies. Modeling studies suggest that both peptides present a tyrosyl and an arginyl residue on the same face of a right-handed helical fold with elliptical cross-section.
Nelson
J
J
Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, The Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, United Kingdom.
Scott
W N
WN
Allen
W E
WE
Wilson
D J
DJ
Harriott
P
P
McFerran
N V
NV
Walker
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D017474:Receptors, Laminin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D009842:Oligopeptides; D010446:Peptide Fragments; D017474:Receptors, Laminin; C101875:epidermal growth factor (33-42); C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; D004815:Epidermal Growth Factor; D015287:Neurokinin B; C038393:neuromedin B