IRS4

IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein has been shown to associate with cytoplasmic signalling molecules that contain SH2 domains. The IRS4 protein is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation. [provided by RefSeq]

Full Name

insulin receptor substrate 4

Function

Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2.

Biological Process

Insulin receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc

Cellular Location

Cell membrane

Involvement in disease

Hypothyroidism, congenital, non-goitrous, 9 (CHNG9):
A form of central hypothyroidism, a disorder characterized by sub-optimal thyroid hormone secretion, due to insufficient stimulation by thyrotropin of an otherwise normal thyroid gland. It may be caused by congenital or acquired disorders of the pituitary gland or hypothalamus. CHNG9 is a congenital, X-linked recessive form. Patients have a small thyroid gland with low free T4 levels and inappropriately normal levels of thyrotropin.

PTM

Phosphorylated on tyrosine residues in response to both insulin and IGF1 signaling. Phosphorylated on Tyr-921 in response to FGF2 signaling. Phosphorylation of Tyr-921 is required for GRB2, phospholipase C-gamma and phosphatidylinositol 3-kinase interaction.