Research article summary (published 30 May 2009):

Role of the C-terminal linear region of EGF-like growth factors in ErbB specificity.

Full Abstract

The epidermal growth factor (EGF)-like growth factors bind their ErbB receptors in a highly selective manner. Recently, we have shown that the sequence YYDLL in the C-terminal linear region is compatible with binding to all ligand-binding ErbB receptors. In the present study, we show that introduction of the YYDLL sequence into the ErbB1 specific ligands EGF and transforming growth factor-alpha (TGFalpha) broadened their receptor specificity towards ErbB4. Upon introduction of the YYDLL sequence into epiregulin, which by itself binds ErbB1 and ErbB4 but not ErbB3, its binding specificity was broadened to ErbB3, concomitant with enhanced affinity for ErbB4. Introduction of the YYDLL sequence into NRG1beta resulted in a 10-fold increase in affinity for ErbB3, without affecting its receptor specificity. Remarkably, the strongly enhanced affinity for ErbB3 negatively influenced their mitogenic activity towards cells coexpressing ErbB2 and ErbB3. These observations are discussed in terms of the optimised ErbB affinity, selectivity and mitogenic potential that have taken place during evolution.

Author information

Author/s: van der Woning, Sebastian P (SP); Venselaar, Hanka (H); van Rotterdam, Walter (W); Jacobs-Oomen, Saskia (S); van Leeuwen, Jeroen E M (JE); van Zoelen, Everardus J J (EJ);

Affiliation: Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Growth factors (Chur, Switzerland) (Growth Factors), published in England. (Language: eng)

Reference: 2009-Jun; vol 27 (issue 3) : pp 163-72

Dates: Created 2009/05/13; Completed 2009/07/29;

PMID: 19384683, status: MEDLINE (last retrieval date: 8/20/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amino Acid Motifs - physiology Amino Acid Sequence Animals Cell Line Cell Proliferation Epidermal Growth Factor - metabolism Genes, erbB-1 - physiology Humans

Humans Mice Molecular Sequence Data Neuregulin-1 - metabolism Protein Binding Receptor, Epidermal Growth Factor - metabolism Receptor, erbB-2 - metabolism Transforming Growth Factor alpha - metabolism

Associated Chemicals: Erbb2 protein, mouse (0) ; Neuregulin-1 (0) ; Transforming Growth Factor alpha (0) ; epiregulin (0) ; Epidermal Growth Factor (62229-50-9) ; ERBB4 protein (EC 2.7.1.112) ; Receptor, Epidermal Growth Factor (EC 2.7.1.112) ; Receptor, erbB-2 (EC 2.7.1.112)

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