IRS4
IRS4 (insulin receptor substrate 4, also known as PY160 and IRS-4) is a cell membrane-associated adaptor protein that links growth factor receptors with tyrosine kinase activity to intracellular signalling molecules containing SH2 domains. It belongs to the insulin receptor substrate family. Browse Assay Genie's current range of IRS4 research reagents below, or read on for the biology behind the target.
IRS4 acts as an interface between multiple growth factor receptors that possess tyrosine kinase activity, such as the insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signalling molecules containing SH2 domains. It is involved in the IGF1R mitogenic signalling pathway. During insulin stimulation, IRS4 promotes the AKT1 signalling pathway and BAD phosphorylation, without activating RPS6KB1 or inhibiting apoptosis. Its interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity.
The IRS4 gene encodes a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein associates with cytoplasmic signalling molecules that contain SH2 domains, and it is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation. UniProt lists its subcellular location as the cell membrane, and the mouse ortholog is Irs4.
Beyond insulin signalling, IRS4 may be involved in nonreceptor tyrosine kinase signalling in myoblasts and plays a pivotal role in the proliferation and differentiation of hepatoblastoma cells through EPHB2 activation upon IGF1 stimulation. It may also contribute to signal transduction in response to IL4 and GH on mitogenesis, to a lesser extent than insulin. Functionally, it has a role in growth, reproduction and glucose homeostasis. IRS4 may also act as a negative regulator of IGF1 signalling by suppressing the function of IRS1 and IRS2, making it a useful point of comparison within the insulin receptor substrate family.
IRS4 is phosphorylated by the insulin receptor and promotes AKT1 signalling and BAD phosphorylation during insulin stimulation.
IRS4 participates in IGF1R mitogenic signalling and may negatively regulate IGF1 signalling by suppressing IRS1 and IRS2.
IRS4 is implicated in hepatoblastoma cell proliferation and differentiation through EPHB2 activation following IGF1 stimulation.
IRS4 plays a role in growth, reproduction and glucose homeostasis, relevant to metabolic and endocrine signalling studies.
IRS4 acts as an interface between receptors with tyrosine kinase activity, including the insulin receptor, IGF1R and FGFR1, and intracellular SH2 domain-containing signalling molecules. It promotes AKT1 signalling during insulin stimulation and plays a role in growth, reproduction and glucose homeostasis.
The HGNC-approved name is insulin receptor substrate 4, and the gene symbol is IRS4. Recorded aliases are PY160 and IRS-4. The protein is a member of the insulin receptor substrate family, alongside IRS1 and IRS2.
A mouse ortholog, Irs4, is recorded for the human gene. UniProt notes that IRS4 may negatively regulate IGF1 signalling by suppressing IRS1 and IRS2, so the family is often studied together. Check the datasheet of any product for its validated reactivity.
Other insulin receptor substrate family members that IRS4 may regulate within insulin and IGF1 signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O14654; product specifications from Assay Genie datasheets.