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A NOVEL TRANSFORMING PROTEIN (SHC) WITH AN SH2 DOMAIN IS IMPLICATED IN MITOGENIC SIGNAL TRANSDUCTION
Author(s): PELICCI G, LANFRANCONE L, GRIGNANI F, MCGLADE J, CAVALLO F, FORNI G, NICOLETTI I, GRIGNANI F, PAWSON T, PELICCI PG
Source: CELL    Volume: 70    Issue: 1    Pages: 93-104    Published: JUL 10 1992  
Times Cited: 1,059     References: 57     
Abstract: A new SH2-containing sequence, SHC, was isolated by screening cDNA libraries with SH2 representative DNA probes. The SHC cDNA is predicted to encode overlapping proteins of 46.8 and 51.7 kd that contain a single C-terminal SH2 domain, and an adjacent glycine/proline-rich motif with regions of homology with the alpha-1 chain of collagen, but no identifiable catalytic domain. Anti-SHC antibodies recognized three proteins of 46, 52, and 66 kd in a wide range of mammalian cell lines. These SHC proteins complexed with and were phosphorylated by activated epidermal growth factor receptor. The physical association of SHC proteins with activated receptors was recreated in vitro by using a bacterially expressed SHC SH2 domain. NIH 3T3 mouse fibroblasts that constitutively overexpressed SHC acquired a transformed phenotype in culture and formed tumors in nude mice. These results suggest that the SHC gene products couple activated growth factor receptors to a signaling pathway that regulates the proliferation of mammalian cells.
Document Type: Article
Language: English
Reprint Address: PELICCI, G (reprint author), UNIV PERUGIA, MONTELUCE POLICLIN, IST CLIN MED 1, I-06100 PERUGIA, ITALY
Addresses:
1. MT SINAI HOSP, SAMUEL LUNENFELD RES INST, DIV MOLEC & DEV BIOL, TORONTO M5G 1X5, ONTARIO CANADA
2. UNIV TURIN, IST MICROBIOL, I-10126 TURIN, ITALY
Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138
Subject Category: Biochemistry & Molecular Biology; Cell Biology
IDS Number: JC957
ISSN: 0092-8674
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