The SHC gene encodes a
signaling and transforming protein containing Src homology 2 and 3 (SH2
and SH3) domains. The SHC gene encodes 2 widely expressed overlapping
proteins of 46 and 52 kD, both containing a C-terminal SH2 domain (Pelicci et al.,
1992). Adjacent to the SH2 region is a glycine- and proline-rich
region. The 2 proteins differ in their N terminals. SHC proteins are
involved in mitogenic signal transduction and act by coupling growth
factor receptors to the RAS (see 190020)
signaling pathway. The protein encoded by the SHC1 gene is thought to act
as an adaptor in many signal transduction pathways, for example,
facilitating the activation of RAS proteins in response to a variety of
factors (Yulug et al., 1995). SHC proteins are rapidly associated
with and phosphorylated by growth factor receptors with intrinsic tyrosine
kinase activity (McGlade et al., 1992). 
In addition to p52 and p46, a
66-kD protein is also encoded by the SHC locus. p66 shares the SH2 domain,
a collagen homology domain, and a phosphotyrosine-binding domain. However,
p66 contains a unique N-terminal region. Like p52 and p46, p66 becomes
tyrosine phosphorylated upon activation of growth factor receptors and
forms stable complexes with GRB2 (108355),
an adaptor protein for the RAS exchange factor SOS (see 182530).
However, it does not affect mitogen-activated protein kinase activity
(MAPK) and inhibits c-fos (164810)
promoter activation, indicating that p66 may not be involved in RAS
activation.
