Ligand-independent signaling by a tumor-associated isoform of ErbB4

Sundvall, M., Maatta, J. A., Peri, L., Junttila, T. T., Egeblad, M., Elenius, K. (December 2004) Ligand-independent signaling by a tumor-associated isoform of ErbB4. Cancer Research, 64 (7 Supp). p. 23. ISSN 1078-0432

URL: http://cancerres.aacrjournals.org/content/64/7_Sup...

Abstract

ErbB/HER growth factor receptor family includes members with well-characterized transforming potential. However, the role of ErbB4 as a human oncogene has remained controversial. Here, signaling characteristics of four recently characterized isoforms of ErbB4 were determined. All four isoforms were functional, as demonstrated by enhanced receptor tyrosine phosphorylation, cellular DNA synthesis and survival in response to ligand stimulation. One of the four isoforms, ErbB4 JM-a CYT-2, however, promoted survival and anchorage-independent cancer cell growth also in the absence of exogenous ligands. The novel ligand-independent signaling mechanism was dependent on constitutive receptor phosphorylation and proteolytic generation of an intracellular receptor fragment resistant to proteasomal degradation. These findings demonstrate that distinct ErbB4 isoforms activate qualitatively and quantitatively different signaling pathways, and suggest that the isoform ErbB4 JM-a CYT-2, known to be overexpressed in human malignancies, specifically regulates cellular responses relevant for malignant transformation. These observations indicate that different ErbB4 isoforms may be of differential clinical potential in cancer therapy and prognostics.

Item Type: Paper
Additional Information: Meeting Abstract
Subjects: diseases & disorders > cancer
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
CSHL Authors:
Communities: CSHL labs > Egeblad lab
Depositing User: Matt Covey
Date: December 2004
Date Deposited: 14 Mar 2013 19:38
Last Modified: 05 Jan 2017 21:18
URI: http://repository.cshl.edu/id/eprint/27810

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