A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction

Giuliana Pelicci, Luisa Lanfrancone, Francesco Grignani, Jane McGlade, Federica Cavallo, Guido Forni, Ildo Nicoletti, Fausto Grignani, Tony Pawson, Pier Giuseppe Pelicci

Research output: Contribution to journalArticlepeer-review

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 α1 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.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalCell
Volume70
Issue number1
DOIs
Publication statusPublished - 10 Jul 1992
Externally publishedYes

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