Transcriptional down-regulation of epidermal growth factor receptors by nerve growth factor treatment of PC12 cells

Makoto Shibutani, Philip Lazarovici, Alfred C. Johnson, Yasuhiro Katagiri, Gordon Guroff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Treatment of PC12 cells with nerve growth factor leads to a decrease in the number of epidermal growth factor receptors on the cell membrane. The mRNA for the epidermal growth factor receptor decreases in a comparable fashion. This decrease appears due to a decrease in the transcription of the epidermal growth factor receptor gene because first, there is no difference in the stability of the epidermal growth factor receptor mRNA, second, newly transcribed epidermal growth factor receptor mRNA is decreased in nerve growth factor-differentiated cells, and third, constructs containing the promoter region of the epidermal growth factor receptor gene are transcribed much less readily in nerve growth factor-differentiated cells than in untreated cells. The decreases in mRNA are not seen in the p140(trk)- deficient variant PC12nnr5 cells nor in cells containing either dominant- negative Ras or dominant-negative Src. Treatment with nerve growth factor also increases the cellular content of GCF2, a putative transcription factor inhibitory for the transcription of the epidermal growth factor receptor gene. The increase in GCF2, like the decrease in the epidermal growth factor receptor mRNA, is not seen in PC12nnr5 cells nor in cells expressing either dominant-negative Ras or dominant-negative Src. The results suggest that nerve growth factor-induced down-regulation of the epidermal growth factor receptor is under transcriptional control, is p140(trk)-, Ras-, and Src- dependent, and may involve transcriptional repression by GCF2.

Original languageEnglish
Pages (from-to)6878-6884
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number12
DOIs
StatePublished - 20 Mar 1998

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