Growth stimulation expressed gene 2 protein (ST2)

Growth stimulation expressed gene 2 (ST2), also known as T1, IL1RL1 or Fit1, is a member of the interleukin-1 (IL-1) receptor superfamily. It is mainly divided into two types: trans-membrane ST2 (trans-membrane ST2, ST2L) and soluble ST2 (soluble ST2, sST2). Interleukin 33 (IL-33) is its endogenous ligand, and the IL-33/ST2L pathway has a variety of cardiovascular protective effects such as anti-atherosclerosis, anti-myocardial hypertrophy, anti-myocardial fibrosis, etc., whereas sST2, as a kind of deceptive receptor, binds to IL-33 and blocks the above biological effects. sST2, as a new type of biomarker, plays an important role in the diagnosis and treatment of cardiovascular diseases. It plays an important role in the diagnosis and treatment of many cardiovascular diseases. ST2 is closely related to the severity of heart failure and can be an important prognostic indicator of heart failure and myocardial infarction.

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The inventory of reagents associated with Growth stimulation expressed gene 2 (ST2) that KMD Bioscience can offer:

VD Family

Growth STimulation expressed gene 2 (ST2) is a member of the interleukin 1 receptor/Toll-like receptor superfamily, and has two main isoforms: (i) transmembrane ST2 (ST2L), which has a transmembrane structure containing a transmembrane fragment and an intracellular structural domain of Toll/IL-1TR receptor; and (ii) soluble ST2 (ST2L), which has a transmembrane structure containing a transmembrane fragment and an intracellular structural domain of Toll/IL-1TR receptor. ST2 is not an "orphan receptor" and its specific ligand is interleukin-33 (IL-33); ST2 is mainly expressed in cardiomyocytes, reflecting ventricular wall stress, and its detection is independent of age, sex, and body mass index, making it an excellent marker of acute and chronic heart failure. excellent marker for acute and chronic heart failure. Four subtypes of ST2 are known: sST2, ST2L, ST2V, and ST2LV. sST2L is a transmembrane ST2 with an overall structure similar to that of the type I IL-1 receptor, including an extracellular structural domain (3 linked immunoglobulin-like modules), a transmembrane fragment, and an intracellular structural domain of Toll/IL-1R. sST2 is a soluble ST2 lacking both transmembrane and intracellular domains. transmembrane and intracellular structural domains and includes a unique sequence consisting of a 9-amino acid C-terminus that can be detected in serum. sST2V and sST2LV are the two spliceosomes of ST2L. The most common of its four isoforms are sST2 (IL1RL1-a) and ST2L (IL1RL1-b). sST2 and ST2L are derived from a dual promoter that promotes differential expression of mRNAs. Different splicing of the promoter and different processing of the 3′end of the same mRNA are responsible for the generation of sST2 and ST2L [4]. sST2 genes have two promoters: a proximal promoter and a distal promoter, which are capable of influencing the gene's transcriptional regulation mechanism.

Figure 1 Schematic diagram of the molecular structure of ST2

Biological functions of ST2

IL-33 is the endogenous ligand of ST2. IL-33, a member of the IL-1 family, is a bifunctional protein that can be transported out of the cell to bind to membrane receptors on target cells and then mediate downstream signaling pathways; it can also be transported to target cells and localized in the nucleus to function as a DNA binding factor. It is also thought to regulate mRNA transcription of ST2L and sST2 itself. Studies have confirmed that IL-33 is a paracrine signaling molecule between cardiomyocytes and fibroblasts, and its expression is up-regulated under increased circulating tension.IL-33/ST2 signaling is a mechanistically-activated fibroblast-cardiomyocyte paracrine system, which has cardioprotective effects, including slowing down the onset of atherosclerosis, resisting myocardial fibrosis, and reducing necrosis of myocardial cells; and sST2 acts as a "decoy" to the cardiomyocytes, which is the most important factor in the development of cardiomyocytes. sST2, as a "decoy receptor", can block the biological effects of IL-33/ST2L by binding to the ligand IL-33, which exerts its cellular functions by binding to the receptor complex composed of ST2L and IL-1RAcP, which is a co-receptor. 1RAcP, a co-receptor protein, linked to ST2 in a ligand-dependent manner enhances the affinity of IL-33 for ST2L, is essential for IL-33 signaling through ST2L, and IL-33-mediated signaling can be inhibited by elimination of IL-1RAcP. When secreted IL-33 binds to the heterodimeric ST2L/IL-1RAcP receptor complex it can activate it, transducing the signal into the cell and activating downstream mitogen-activated protein kinase (MAPKK) via a series of downstream signaling molecules such as Myeloid Differentiation Factor 88 (MyD88), IL-1 Receptor-Related Kinase (IRAK), and Tumor Necrosis Factor Receptor-Related Factor 6 (TRAF6), which activates downstream mitogen-activated protein kinase (MAPKK), activated MAPKK kinase can activate protein-1 (AP-1) through c-jun amino-terminal kinase (JNK); at the same time, TRAF6 can also activate the nuclear factor-κB (NK-κB) kinase inhibitor complex, so that NK-κB is released from the complex, which ultimately results in the production of Th2 effector cytokines IL-4, IL-5, and IL-13, and the biological functions. fulfill biological functions.

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