Role of binding ligand in toxic hybrid proteins: a comparison of EGF-ricin, EGF-ricin A-chain, and ricin
To analyze the influence of ricin B-chain on (i) the toxicity of hybrid-protein conjugates, (ii) the rate of cellular uptake of conjugates, and (iii) the rate at which ricin A-chain (RTA) is delivered to the cytoplasm, toxic hybrid proteins have been constructed consisting of epidermal growth factor (EGF) coupled in disulfide linkage either to ricin or to RTA. EGF-ricin is no more toxic on A431 cells than EGF-RTA. The two conjugates demonstrate similar kinetics of cellular uptake (defined as antibody irreversible toxicity). EGF-RTA and EGF-ricin, like ricin, required a 2-2 1/2 hour period at 37/sup 0/ before the onset of protein synthesis inhibition occurred. Results suggest that (i) RTA determines the processes which carry it, either in conjugate or toxin, from the plasma membrane binding site to the cytoplasm following endocytosis, and (ii) the ricin B chain is not required for these processes.
- Research Organization:
- UCLA School of Medicine, Los Angeles
- DOE Contract Number:
- AC03-76SF00012
- OSTI ID:
- 5910435
- Journal Information:
- Biochem. Biophys. Res. Commun.; (United States), Journal Name: Biochem. Biophys. Res. Commun.; (United States) Vol. 124:2; ISSN BBRCA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANTIGENS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
CELL CONSTITUENTS
CHEMICAL BONDS
CYTOPLASM
INHIBITION
KINETICS
LIGANDS
MATERIALS
MOLECULAR STRUCTURE
ORGANIC COMPOUNDS
PROTEINS
REACTION KINETICS
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
SYNTHESIS
TOXIC MATERIALS
TOXICITY
TOXINS
UPTAKE