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PMID:6315706

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Citation

Massagué, J (1983) Epidermal growth factor-like transforming growth factor. II. Interaction with epidermal growth factor receptors in human placenta membranes and A431 cells. J. Biol. Chem. 258:13614-20

Abstract

A 125I-labeled derivative of rat epidermal growth factor-like transforming growth factor (125I-eTGF) that retains the chemical and biological properties of native eTGF has been prepared to characterize the interaction of eTGF with epidermal growth factor (EGF) membrane receptors. Binding of 125I-eTGF and 125I-labeled mouse EGF (125I-EGF) to membrane preparations from human placenta and the A431 human epidermoid carcinoma cell line was competed for to the same extent and with the same potency by either unlabeled eTGF or EGF. Components of placenta membranes and A431 membranes (145-170 kDa) were the major species affinity-labeled by cross-linking with membrane-bound 125I-eTGF or 125I-EGF. Affinity labeling of these receptor species was fully inhibited by both native eTGF and native EGF when present in excess during incubation of membranes with 125I-eTGF or 125I-EGF. The binding affinity and capacity of receptors in A431 membranes and placenta membranes were strikingly similar for eTGF and EGF. However, binding of 125I-eTGF to membrane receptors was highly sensitive to pH, being optimal only within the pH 8.0-8.5 range whereas EGF binding was optimal at pH 7.0-9.0. eTGF binding and EGF binding were modified in parallel by exposure of placental membranes to phytohemagglutinin, concanavalin A, or wheat germ agglutinin. Prolonged exposure of A431 cells to eTGF or EGF induced the same extent of down-regulation of both eTGF binding and EGF binding. eTGF-induced down-regulation of receptors in A431 cells followed the same kinetics as EGF-induced receptor down-regulation. The data indicate that despite the limited sequence homology between eTGF and EGF, these two ligands exhibit a remarkably similar mode of interaction with a common eTGF/EGF membrane receptor type.

Links

PubMed

Keywords

Carcinoma, Squamous Cell/metabolism; Cell Line; Cell Membrane/metabolism; Epidermal Growth Factor/metabolism; Female; Humans; Kinetics; Peptides/metabolism; Placenta/metabolism; Pregnancy; Receptor, Epidermal Growth Factor; Receptors, Cell Surface/metabolism; Transforming Growth Factors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:EGF

enables

GO:0005154: epidermal growth factor receptor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:EGF

acts_upstream_of_or_within

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TGFA

enables

GO:0005154: epidermal growth factor receptor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TGFA

involved_in

GO:0007173: epidermal growth factor receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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