The Internal Revenue Service (IRS) is the revenue service of the United States federal government. The government agency is a bureau of the Department of the Treasury, and is under the immediate direction of the Commissioner of Internal Revenue. The IRS is responsible for collecting taxes and the administration of the Internal Revenue Code. It has also overseen various benefit programs, and enforces portions of the Affordable Care Act.
The first income tax was assessed in 1862 to raise funds for the American Civil War, with a rate of 3%. Today the IRS collects over $2.4 trillion each tax year. It processes around 234 million tax returns annually.
In July 1862, during the Civil War, President Abraham Lincoln and Congress created the office of Commissioner of Internal Revenue and enacted a temporary income tax to pay war expenses (see Revenue Act of 1862). The position of Commissioner exists today as the head of the Internal Revenue Service.
Insulin receptor substrate 4 is a protein that in humans is encoded by the IRS4 gene.
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.
IRS4 has been shown to interact with CRK and NISCH.
Insulin receptor substrate 1 (IRS-1) is a signalling adapter protein that in humans is encoded by the IRS-1 gene. It contains a single pleckstrin homology (PH) domain at the N-terminus and a PTB domain ca. 40 residues downstream of this. Together with IRS2, IRS3 (pseudogene) and IRS4, it is homologous to the Drosophila protein chico, whose disruption extends the median lifespan of flies up to 48%. Similarly, Irs1 mutant mice experience moderate life extension and delayed age-related pathologies.
Insulin receptor substrate 1 plays a key role in transmitting signals from the insulin and insulin-like growth factor-1 (IGF-1) receptors to intracellular pathways PI3K / Akt and Erk MAP kinase pathways.
Tyrosine phosphorylation of the insulin receptors or IGF-1 receptors, upon extracellular ligand binding, induces the cytoplasmic binding of IRS-1 to these receptors, through its PTB domains. Multiple tyrosine residues of IRS-1 itself are then phosphorylated by these receptors. This enables IRS-1 to activate several signalling pathways, including the PI3K pathway and the MAP kinase pathway.