MST1 信号
中文名称
通路描述
炎症介质如巨噬细胞产生的生长因子在细菌感染、组织损伤和免疫反应中发挥重要作用。许多生长因子及其受体酪氨酸蛋白激酶（RTKs）在炎症、伤口愈合和组织重塑中起关键作用。肝细胞生长因子样蛋白（MST1，也称为巨噬细胞刺激蛋白，MSP）与特定受体结合，该受体为巨噬细胞刺激蛋白受体（MST1R，也称为 RON，南特起源受体）。MST1 属于角蛋白蛋白家族，包括 HGF 和纤溶原。MST1 由肝脏产生，在血液中循环，以生物活性单链前体形式存在（pro-MST1）。pro-MST1 的蛋白酶解为生物活性 MST1 二聚体是受体结合所必需的。蛋白酶解发生在凝血和炎症部位，产生的 MST1 二聚体随后与局部巨噬细胞上的 MST1R 受体结合。MST1R 广泛表达，但主要在上皮细胞中表达。MST1 与 MST1R 的结合促进受体同源二聚化，进而允许催化位点内两个酪氨酸残基的自磷酸化，调节激酶活性并允许受体结合位点的磷酸化。结合位点是下游信号传导所必需的，通过直接和间接结合含有 SH2 结构域的上游信号传导调节蛋白如 GRB2、PI3K 和 SRC 实现。MST1/MST1R 信号传导在调节炎症中发挥双重作用；最初刺激趋化和吞噬作用（巨噬细胞激活），然后对巨噬细胞发挥广泛的抑制作用，限制炎症反应的 extent（Wang 等，2002）。MST1R 在许多上皮癌中上调，被认为在这些癌症的进展中发挥作用（Kretschmann 等，2010）。
英文描述
Signaling by MST1 Inflammatory mediators such as growth factors produced by macrophages play an important role in the inflammatory response occurring during bacterial infection, tissue injury and immune responses. Many growth factors and their receptor-type protein tyrosine kinases (RTKs) play a critical role in inflammation, wound healing and tissue remodelling. The growth factor hepatocyte growth factor-like protein (MST1, also known as macrophage-stimulating protein, MSP) binds to a specific receptor, macrophage-stimulating protein receptor (MST1R, also known as RON, recepteur d'origine nantais). MST1 belongs to the kringle protein family, which includes HGF and plasminogen. It is produced by the liver and circulates in the blood as a biologically-inactive single chain precursor (pro-MST1). Proteolytic cleavage of pro-MST1 into the biologically-active MST1 dimer is necessary for receptor binding. Cleavage occurs during blood coagulation and at inflammatory sites, the resultant MST1 dimer then binds MST1R receptors on local macrophages. MST1R is ubiquitously expressed but mainly in epithelial cells.
MST1 binding to MST1R promotes receptor homodimerisation which in turn allows autophosphorylation of two tyrosine residues within the catalytic site which regulates kinase activity and allows phosphorylation of the carboxy-terminal binding site of the receptor. The docking site is essential for downstream signaling through direct and indirect binding of SH2 domain-containing adaptor proteins such as GRB2, PI3K, and SRC. MST1/MST1R signaling plays a dual role in regulating inflammation; initially stimulating chemotaxis and phagocytosis (macrophage activation) and then exerts broad inhibitory effects on macrophages, limiting the extent of inflammtory responses (Wang et al. 2002). MST1R is upregulated in many epithelial cancers where it is thought to play a role in the progression of these types of cancer (Kretschmann et al. 2010).
MST1 binding to MST1R promotes receptor homodimerisation which in turn allows autophosphorylation of two tyrosine residues within the catalytic site which regulates kinase activity and allows phosphorylation of the carboxy-terminal binding site of the receptor. The docking site is essential for downstream signaling through direct and indirect binding of SH2 domain-containing adaptor proteins such as GRB2, PI3K, and SRC. MST1/MST1R signaling plays a dual role in regulating inflammation; initially stimulating chemotaxis and phagocytosis (macrophage activation) and then exerts broad inhibitory effects on macrophages, limiting the extent of inflammtory responses (Wang et al. 2002). MST1R is upregulated in many epithelial cancers where it is thought to play a role in the progression of these types of cancer (Kretschmann et al. 2010).
所含基因
4 个基因