Format:
Online-Ressource
ISSN:
1460-2075
Content:
Shc proteins are targets of activated tyrosine kinases and are implicated in the transmission of activation signals to Ras. The p46shc and p52shc isoforms share a C‐terminal SH2 domain, a proline‐ and glycine‐rich region (collagen homologous region 1; CH1) and a N‐terminal PTB domain. We have isolated cDNAs encoding for a third Shc isoform, p66shc. The predicted amino acid sequence of p66shc overlaps that of p52shc and contains a unique N‐terminal region which is also rich in glycines and prolines (CH2). p52shc/p46shc is found in every cell type with invariant reciprocal relationship, whereas p66shc expression varies from cell type to cell type. p66shc differs from p52shc/p46shc in its inability to transform mouse fibroblasts in vitro. Like p52shc/p46shc, p66shc is tyrosine‐phosphorylated upon epidermal growth factor (EGF) stimulation, binds to activated EGF receptors (EGFRs) and forms stable complexes with Grb2. However, unlike p52shc/p46shc it does not increase EGF activation of MAP kinases, but inhibits fos promoter activation. The isolated CH2 domain retains the inhibitory effect of p66shc on the fos promoter. p52shc/p46shc and p66shc, therefore, appear to exert different effects on the EGFR‐MAP kinase and other signalling pathways that control fos promoter activity. Regulation of p66shc expression might, therefore, influence the cellular response to growth factors.
In:
volume:16
In:
number:4
In:
year:1997
In:
pages:706-716
In:
extent:11
In:
European Molecular Biology Organization, The EMBO journal, Heidelberg : EMBO Press, 1982-, 16, Heft 4 (1997), 706-716 (gesamt 11), 1460-2075
Language:
English
DOI:
10.1093/emboj/16.4.706
URN:
urn:nbn:de:101:1-2023112706324593458745
URL:
https://doi.org/10.1093/emboj/16.4.706
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023112706324593458745
URL:
https://d-nb.info/1311254404/34
URL:
https://doi.org/10.1093/emboj/16.4.706
Bookmarklink