Attenuated processing of epidermal growth factor in the face of marked degradation of transforming growth factor-α

M. Korc, J. E. Finman

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Abstract

T3M4 human pancreatic carcinoma cells avidly bound and internalized 125I-labeled epidermal growth factor (EGF) but did not readily degrade the ligand. Pulse-chase experiments in which the cell-bound radioactivity was allowed to dissociate into the incubation medium in the presence of unlabeled EGF indicated that the majority of the released 125I-EGF consisted of intact EGF and a slightly processed species that readily bound to the cell. Omission of unlabeled EGF during the chase period markedly decreased the amount of radioactivity in the incubation medium, mainly as a result of the rebinding of EGF to the cells. In contrast, T3M4 cells readily degraded 125I-labeled transforming growth factor-α (TGF-α), and the released radiolabeled products did not rebind to the cells. Both ligands were released from T3M4 cells under acidic conditions, complete dissociation occurring at a pH of 4.5 for EGF, and a pH of 6.5 for TGF-α. A431 human epidermoid carcinoma cells and ASPC-1 human pancreatic carcinoma cells also failed to extensively degrade 125I-EGF, whereas Rat-1 fibroblasts markedly degraded the growth factor. As in the case of T3M4 cells, ASPC-1 cells extensively degraded 125I-TGF-α. Degradation of either ligand was blocked by the lysosomotropic compound methylamine in all the tested cell lines. Immunoprecipitation of the EGF receptor with specific polyclonal antibodies and Western blot analysis revealed the anticipated 170-kDa protein in T3M4 cells. Both EGF and TGF-α enhanced EGF receptor degradation, but TGF-α was less effective than EGF. These findings indicate that in certain cell types EGF and TGF-α may be differentially processed.

Original languageEnglish (US)
Pages (from-to)14990-14999
Number of pages10
JournalJournal of Biological Chemistry
Volume264
Issue number25
StatePublished - Jan 1 1989

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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