Characterization of a saporin mitotoxin specifically cytotoxic to cells bearing the granulocyte-macrophage colony-stimulating factor receptor.
When granulocyte-macrophage colony-stimulating factor (GM-CSF) is chemically conjugated to the ribosome-inactivating protein saporin, the resulting protein conjugate is highly toxic for cells expressing the GM-CSF receptor. Structural and Western blot analyses of the purified conjugate establish that it contains equimolar amounts of the starting materials and is free of any contamination by the non-conjugated components. The resulting bifunctional reagent is specifically cytotoxic to cells expressing the GM-CSF receptor, but is ineffective to cells that do not express the receptor. The cytotoxic activity is inhibited in a dose-dependent manner by GM-CSF, but not by any one of five other peptide growth factors. This is the first report of a mitotoxin for cells that express the GM-CSF receptor and which promises to be a valuable tool to study the expression of the GM-CSF receptor in normal and pathological states.
Lappi
D A
DA
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
Martineau
D
D
Sarmientos
P
P
Garofano
L
L
Aranda
A P
AP
Miyajima
A
A
Kitamura
T
T
Baird
A
A
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000302:isolation & purification; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D000922:Immunotoxins; D051379:Mice; D008934:Mitogens / Q000008:administration & dosage; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000008:administration & dosage / Q000633:toxicity*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects*; D054789:Ribosome Inactivating Proteins, Type 1; D012270:Ribosomes / Q000187:drug effects; D000076985:Saporins
D003432:Cross-Linking Reagents; D000922:Immunotoxins; D008934:Mitogens; D010940:Plant Proteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D054789:Ribosome Inactivating Proteins, Type 1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009699:N-Glycosyl Hydrolases; D000076985:Saporins