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.
|Titolo:||A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction|
PELICCI, PIER GIUSEPPE (Primo)
|Parole Chiave:||3T3 Cells; Animals; Amino Acid Sequence; Mice; Adaptor Proteins, Vesicular Transport; Molecular Weight; Shc Signaling Adaptor Proteins; Base Sequence; Sequence Alignment; Adaptor Proteins, Signal Transducing; Transformation, Genetic; Mitosis; Molecular Sequence Data; Proteins; Signal Transduction; Cell Line|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||10-lug-1992|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/0092-8674(92)90536-L|
|Appare nelle tipologie:||01 - Articolo su periodico|