An alternatively processed mRNA from the avian c-erbB gene encodes a soluble, truncated form of the receptor that can block ligand-dependent transformation

Thomas W. Flickinger, Nita Jane Maihle, Hsing Jien Kung

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

At least four major transcripts are produced by the avian c-erbB/epidermal growth factor receptor gene. cDNAs corresponding to the smallest one, a 2.6-kb transcript, were isolated from an adult chicken liver cDNA library. Sequence analysis revealed that the 3′ end of one cDNA clone diverged from the known sequence of the extracellular ligand-binding domain (LBD) of the full-length receptor. A genomic DNA subfragment that contained this unique 3′ divergent end was isolated. Sequence analysis of this genomic DNA fragment revealed that the 2.6-kb c-erbB transcript is produced by alternative processing. Translation of this 2.6-kb transcript would produce a secreted, truncated receptor molecule which contains the amino-terminal three-fourths of the extracellular LBD of the native receptor. COS1 cells and primary chicken embryo fibroblast cells were transfected with expression vectors that contained the 2.6-kb c-erbB cDNA. Conditioned medium from these transfected cells contained a 70-kDa protein that was specifically immunoprecipitated by a polyclonal antiserum directed against the LBD of the avian c-erbB gene product. The 70-kDa truncated receptor could be coimmunoprecipitated from conditioned medium of transfected COS1 cells that was supplemented with recombinant human transforming growth factor alpha (TGFα) by a monoclonal antibody against human TGFα. Additionally, transfected chicken embryo fibroblast cells that overexpressed the 70-kDa truncated receptor were blocked in their ability to form TGFα-dependent colonies in soft agar. These data suggest that the secreted, truncated receptor encoded by the 2.6-kb c-erbB transcript can bind to TGFα and may play an important growth-regulatory function in vitro.

Original languageEnglish (US)
Pages (from-to)883-893
Number of pages11
JournalMolecular and Cellular Biology
Volume12
Issue number2
DOIs
StatePublished - Jan 1 1992

Fingerprint

erbB Genes
Ligands
Messenger RNA
Chickens
Transforming Growth Factor alpha
Complementary DNA
Conditioned Culture Medium
Embryonic Structures
Fibroblasts
erbB-1 Genes
Gene Library
DNA Sequence Analysis
Agar
Sequence Analysis
Immune Sera
Clone Cells
Monoclonal Antibodies
Liver
DNA
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

An alternatively processed mRNA from the avian c-erbB gene encodes a soluble, truncated form of the receptor that can block ligand-dependent transformation. / Flickinger, Thomas W.; Maihle, Nita Jane; Kung, Hsing Jien.

In: Molecular and Cellular Biology, Vol. 12, No. 2, 01.01.1992, p. 883-893.

Research output: Contribution to journalArticle

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