Affinity labeling of a transforming growth factor receptor that does not interact with epidermal growth factor.

Abstract

Membrane components that interact with epidermal growth factor (EGF) and transforming growth factors (TGFs) have been identified by covalent crosslinking to their respective 125I-labeled ligands. Under appropriate conditions, disuccinimidyl suberate or hydroxysuccinimidyl p-azidobenzoate cross-link receptor-bound 125I-labeled EGF to a 140- to 170-kilodalton (kDal) receptor species in membranes from both A431 human carcinoma cells and normal rat kidney cells. 125I-Labeled sarcoma growth factor (SGF), a TGF from virally transformed mouse 3T3 cells, also can be affinity-crosslinked to the 140- to 170-kDal EGF receptor species in membranes from A431 and rat kidney cells. The labeling of this receptor is inhibited when either excess unlabeled EGF or SGF is present during incubation of membranes with either 125I-labeled EGF or 125I-labeled SGF. In contrast, a second receptor species of 60 kDal is affinity-labeled with 125I-labeled SGF but not with 125I-labeled EGF in membranes from both A431 and rat kidney cells. SGF and a TGF from virally transformed rat embryo cells inhibit the labeling of the 60-kDal species when present in excess during incubation of membranes with 125I-labeled SGF, whereas EGF is completely ineffective in inhibiting the labeling of this receptor. The data suggest that a specific 60-kDal receptor that displays high affinity for TGFs but not for EGF may mediate induction of the transformed phenotype. In addition, SGF and other TGFs interact with the 140- to 170-kDal EGF receptor that appears to mediate normal cell growth effects.

• Authors: J Massague, M P Czech, K Iwata, J E DeLarco, G J Todaro
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 79 Issue 22 Pg. 6822-6 (Nov 1982) ISSN: 0027-8424 [Print] United States
• PMID: 6294655 (Publication Type: Journal Article)

Chemical References

• Affinity Labels
• Peptides
• Receptors, Cell Surface
• Epidermal Growth Factor
• Transforming Growth Factors
• ErbB Receptors

Topics

• Affinity Labels (pharmacology)
• Animals
• Carcinoma
• Cell Line
• Cell Transformation, Neoplastic
• Epidermal Growth Factor (metabolism)
• ErbB Receptors
• Humans
• Kidney
• Peptides (metabolism)
• Rats
• Receptors, Cell Surface (isolation & purification, metabolism)
• Transforming Growth Factors