Unlocking The Potential of IRAK1: A Protein Target for Drug Development

Target Name: IRAK1

NCBI ID: G3654

Unlocking The Potential of IRAK1: A Protein Target for Drug Development

The protein known as IRAK1 has garnered significant attention in the scientific community due to its involvement in various cellular processes. IRAK1, which stands for Interactin Receptor kinase 1, is a protein that is expressed in various tissues throughout the body, including the brain, heart , and kidneys1. It is a member of the tyrosine kinase family and is involved in the regulation of cell signaling pathways2.

domain

The domain structure of IRAK1 includes an N-terminal 伪-helix, a central 尾-page, and a C-terminal domain. The N-terminal 伪-helix is 鈥嬧?媜ne of the most striking features of IRAK1. It is composed of two complementary helices and is right-handed. The central 尾-page is the secondary domain of IRAK1, formed by hydrogen bonds between two helices. The C-terminal domain includes an 伪-helix, a 尾-coil and a trans-parallel 尾-helix, which is connected to the N-terminal 伪-helix and participates in IRAK1 signaling 3.

IRAK1 interaction

IRAK1 is a ligand-binding protein that can bind to various ligands, including hormones, growth factors, and intracellular signaling molecules. Ligand binding of IRAK1 mainly occurs in the N-terminal 伪-helical region. In this region, the active center of IRAK1 binds to ligands, resulting in the regulation of a series of cell signaling pathways4.

Biological functions of IRAK1

IRAK1 plays an important role in various physiological processes. In the nervous system, IRAK1 participates in many signaling pathways, including neuronal proliferation, synaptic transmission and neural circuit establishment. IRAK1 is also involved in intracellular waste transport, including phagocytosis and intracellular transport pathways. In the kidney, IRAK1 is involved in tubular cell proliferation and regeneration, as well as glomerular filtration and tubular response to drugs.

Pharmacological significance of IRAK1

Because IRAK1 plays an important role in many physiological processes, it is considered a potential drug target. Some studies have shown that IRAK1 inhibitors can inhibit the growth of a variety of tumors, including breast, lung and prostate cancer. IRAK1 inhibitors can also improve the filtration function of the kidney and reduce the incidence of proteinuria, which is of great significance in the treatment of kidney disease.

The structure and biological function of IRAK1 make it an important target for drug research. Future research will continue to further investigate the biological functions and pharmacological significance of IRAK1 to develop more effective treatments.

Protein Name: Interleukin 1 Receptor Associated Kinase 1

Functions: Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3

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