SHC1
SHC1 (SHC adaptor protein 1, also known as p66, ShcA or SHC) is a signalling adaptor that couples activated growth factor receptors to intracellular pathways. Its isoforms differ in activity and location, linking receptor tyrosine kinases to Ras or regulating the response to oxidative stress. Browse Assay Genie's current range of SHC1 research reagents below, or read on for the biology behind the target.
SHC1 is a signalling adaptor that couples activated growth factor receptors to downstream signalling pathways. The gene encodes three main isoforms that differ in activity and subcellular location. Once phosphorylated, p46Shc and p52Shc link activated receptor tyrosine kinases to Ras by recruiting the GRB2/SOS complex, and are implicated in the cytoplasmic propagation of mitogenic signals. They may therefore act as initiators of the Ras cascade in various non-neuronal systems.
The longest isoform, p66Shc, does not mediate Ras activation. It is instead involved in pathways that regulate the cellular response to oxidative stress and life span, and its expression has been correlated with life span. p66Shc acts as a downstream target of the tumour suppressor p53 and is indispensable for stress-activated p53 to raise intracellular oxidants, trigger cytochrome c release and induce apoptosis. Unlike the other two isoforms, p46Shc is targeted to the mitochondrial matrix. Several transcript variants encoding different isoforms have been described for the SHC1 gene.
SHC1 takes part in several receptor-specific cascades. It acts in signalling initiated by activated KIT and its ligand KITLG/SCF, and downstream of the angiopoietin receptor TEK/TIE2, where it contributes to endothelial cell migration and sprouting angiogenesis. In oncostatin-M signalling through the type II OSM receptor complex (OSMR and IL6ST), SHC1 is recruited to the OSMR subunit in a JAK1-dependent manner and associates with GRB2, contributing to activation of the Ras/Raf/MAPK pathway. The protein belongs to the SH2 domain containing gene group and was originally named SHC (Src homology 2 domain-containing) transforming protein 1.
SHC1 links activated receptor tyrosine kinases to Ras through GRB2/SOS recruitment, making it a core adaptor for studying mitogenic signal propagation.
The p66Shc isoform regulates the cellular response to oxidative stress and has been correlated with life span, supporting work on redox biology.
p66Shc is a downstream target of p53 and is needed for stress-activated p53 to drive oxidant elevation, cytochrome c release and apoptosis.
SHC1 acts downstream of TEK/TIE2 and regulates endothelial cell migration and sprouting angiogenesis.
SHC1 is a signalling adaptor that couples activated growth factor receptors to downstream pathways. The p46Shc and p52Shc isoforms recruit the GRB2/SOS complex to activate Ras, while p66Shc does not activate Ras and instead regulates the response to oxidative stress and life span.
SHC1 is also known as p66, ShcA and SHC, and was previously named SHC (Src homology 2 domain-containing) transforming protein 1. It has three main isoforms, p46Shc, p52Shc and p66Shc, plus additional transcript variants. Only p46Shc is targeted to the mitochondrial matrix.
Yes. The mouse and rat orthologs are both named Shc1. The human protein is linked to p53-dependent apoptosis and oxidative stress responses through p66Shc, so orthologs are used in related studies; check the datasheet of any product for its validated reactivity.
Receptor partners, Ras pathway components and p53 pathway proteins that act alongside SHC1.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P29353; product specifications from Assay Genie datasheets.