Abstract:
:Members of the epidermal growth-factor-receptor tyrosine-kinase (EGFR) family play important roles both in normal growth regulation/cell differentiation and in the genesis and progression of human neoplasia. In the present study, we analysed distinct heregulin (HRG) signals mediated by the HRG receptors HER3 and HER4. In overexpression cell systems, we demonstrate that HRG-induced transformation by "kinase-impaired" HER3 is dependent on coexpression of kinase active HER2. In cells coexpressing HER2 and HER4, however, both kinases significantly contribute to the HRG-induced mitogenic stimulus. In addition, we show that HER3 is no substrate of HRG-activated HER4. Analysis of EGFR crosstalk in a panel of human carcinoma cell lines revealed mainly HRG-induced activation of HER2/HER3, whereas HER4 activation is also detectable to various extents. Evidence for HRG-induced activation of HER3 and/or HER4 indicates relevance of cell-specific expression patterns of these high- and low-affinity HRG receptors in the modulation of a ligand-induced stimulus. Specific signal modulation and definition can be demonstrated further by distinct time courses of mitogen-activated protein (MAP) kinase (MAPK) activation, which are induced by distinct HRG isotypes via differential binding to HER2/HER3 versus HER2/HER4. In concert, these mechanisms of signal modulation may be decisive for the diverse biological activities of HRG in different cell types.
journal_name
J Cell Physioljournal_title
Journal of cellular physiologyauthors
Weiss FU,Wallasch C,Campiglio M,Issing W,Ullrich Adoi
10.1002/(SICI)1097-4652(199711)173:2<187::AID-JCP1subject
Has Abstractpub_date
1997-11-01 00:00:00pages
187-95issue
2eissn
0021-9541issn
1097-4652pii
10.1002/(SICI)1097-4652(199711)173:2<187::AID-JCP1journal_volume
173pub_type
杂志文章abstract::Human keratinocytes isolated from a skin biopsy and cultured in vitro on a feeder-layer of irradiated fibroblasts reconstitute a stratified squamous epithelium suitable for grafting onto patients suffering from large burn wounds. Since conditioned medium from 3T3-J2 cells can partially substitute for the intact feeder...
journal_title:Journal of cellular physiology
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