| 货号 | APR-031-50ul |
| 描述 | Each antibody ordered from Alomone Labs is supplied with its corresponding control peptide (antigen), free of charge. A Rabbit Polyclonal Antibody to Human Protease-Activated Receptor-1 |
| 反应种属 | H |
| 应用 | IC, IFC, IH, LCI, WB |
| 供应商 | Alomone |
| 背景 | Protease-activated receptor 1 (PAR-1) belongs to a family of four G protein-coupled receptors (PAR-1 - 4) that are activated as a result of proteolytic cleavage by certain serine proteases, hence their name. In this novel modality of activation, a specific protease cleaves the PAR receptor within a defined sequence in its extracellular N-terminal domain. This results in the creation of a new N-terminal tethered ligand, which subsequently binds to a site in the second extracellular loop of the same receptor. This binding results in the coupling of the receptor to G proteins and in the activation of several signal transduction pathways.1-3 Different PARs are activated by different proteases. Hence, PAR-1 is activated by thrombin (and is in fact also known as the thrombin receptor), as are PAR-3 and PAR-4, while PAR-2 is activated by trypsin.1-3 PAR-1 can be also cleaved and activated by other proteases such as plasmin, Factor Xa, cathepsin G, and others. The intramolecular nature of PAR activation and the continuous presence of the tethered ligand that cannot diffuse away imply the existence of several mechanisms for the rapid termination of PAR signaling. Indeed, following receptor activation, there is rapid phosphorylation of the C-terminal end of the receptor, followed by receptor internalization and degradation. In addition, several proteases can cleave away the tethered ligand, thereby “disarming” the PAR.1-3 PAR-1 signals through several G proteins including Gaq, Gai, and Ga12/13, resulting in the activation of several transduction pathways including intracellular Ca2+ mobilization, Rho and Rac signaling, and MAPK activation.1-3 PAR-1 is expressed in several cell types including platelets, leukocytes, vascular endothelial cells, gastrointestinal epithelial cells, myocytes, and neurons. The best studied physiological function of PAR-1 is its involvement in the coagulation cascade. Thrombin, the preeminent ligand of PAR-1, activates the receptor on the surface of platelets, hence inducing platelet aggregation, granular secretion, and procoagulant activity. PAR-1 also plays a crucial role in vascular ontogenesis. Accordingly, PAR-1 knockout mice show bleeding at multiple sites and usually die at mid-gestation.1-3 PAR-1 also plays important roles in tumor growth and metastasis. PAR-1 is upregulated in several human cancers as are several proteases such as plasmin and matrix metalloproteases (MMPs) that act as PAR-1 ligands, thereby creating an autocrine loop. PAR-1 activation in cancer cells transmits mitogenic signals through the activation of the erk1/2 pathway and is involved in tumor spread via its pro-angiogenic activity.4 |
| 运输条件 | Ambient |
| 存放说明 | -20 |
| 纯度 | Affinity purified on immobilized antigen. |
| 参考文献 | 1.MacFarlane, S.R.et al.(2001)Pharmacol. Rev.53, 245. 2.Hollenberg, M.D.et al.(2002)Pharmacol. Rev.54, 203. 3.Ossovskaya, V.S.et al. (2004) Physiol. Rev.84, 579. 4.Arora, P.et al.(2007)J. Cell Sci.120, 921. |
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