Title |
Inhibition of ErbB-2 Mitogenic and Transforming Activity by RALT, a Mitogen-Induced Signal Transducer Which Binds to the ErbB-2 Kinase Domain
|
---|---|
Published in |
Molecular & Cellular Biology, March 2023
|
DOI | 10.1128/mcb.20.20.7735-7750.2000 |
Pubmed ID | |
Authors |
Loredana Fiorentino, Chiara Pertica, Monia Fiorini, Claudio Talora, Marco Crescenzi, Loriana Castellani, Stefano Alemà, Piero Benedetti, Oreste Segatto |
Abstract |
The product of rat gene 33 was identified as an ErbB-2-interacting protein in a two-hybrid screen employing the ErbB-2 juxtamembrane and kinase domains as bait. This interaction was reproduced in vitro with a glutathione S-transferase fusion protein spanning positions 282 to 395 of the 459-residue gene 33 protein. Activation of ErbB-2 catalytic function was required for ErbB-2-gene 33 physical interaction in living cells, whereas ErbB-2 autophosphorylation was dispensable. Expression of gene 33 protein was absent in growth-arrested NIH 3T3 fibroblasts but was induced within 60 to 90 min of serum stimulation or activation of the ErbB-2 kinase and decreased sharply upon entry into S phase. New differentiation factor stimulation of mitogen-deprived mammary epithelial cells also caused accumulation of gene 33 protein, which could be found in a complex with ErbB-2. Overexpression of gene 33 protein in mouse fibroblasts inhibited (i) cell proliferation driven by ErbB-2 but not by serum, (ii) cell transformation induced by ErbB-2 but not by Ras or Src, and (iii) sustained activation of ERK 1 and 2 by ErbB-2 but not by serum. The gene 33 protein may convey inhibitory signals downstream to ErbB-2 by virtue of its association with SH3-containing proteins, including GRB-2, which was found to associate with gene 33 protein in living cells. These data indicate that the gene 33 protein is a feedback inhibitor of ErbB-2 mitogenic function and a suppressor of ErbB-2 oncogenic activity. We propose that the gene 33 protein be renamed with the acronym RALT (receptor-associated late transducer). |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 2% |
Australia | 1 | 2% |
Unknown | 46 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 9 | 19% |
Researcher | 9 | 19% |
Other | 5 | 10% |
Student > Doctoral Student | 4 | 8% |
Student > Master | 4 | 8% |
Other | 10 | 21% |
Unknown | 7 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 17 | 35% |
Agricultural and Biological Sciences | 11 | 23% |
Medicine and Dentistry | 7 | 15% |
Neuroscience | 2 | 4% |
Business, Management and Accounting | 1 | 2% |
Other | 3 | 6% |
Unknown | 7 | 15% |