Plau

Plau Full Name

Plasminogen activator, urokinase

Plau Introduction

PLAU is a key serine protease encoded by the PLAU gene located on the long arm of human chromosome 10 at band 22.2 (10q22.2). The gene spans approximately 6.4 kb and consists of 11 exons. Initially synthesized as an inactive single-chain precursor (pro-uPA) with a molecular weight of about 54 kDa, PLAU is subsequently converted into its active two-chain form via limited proteolytic cleavage, with the chains connected by a disulfide bond. The A-chain contains an EGF-like domain, which specifically binds to the urokinase receptor (uPAR/CD87) on the cell surface, while the B-chain harbors the catalytic domain responsible for activating plasminogen. Notably, PLAU exists in multiple molecular forms, including high-molecular-weight uPA and low-molecular-weight uPA. The latter lacks the EGF-like domain and cannot efficiently bind to the cell membrane receptor. This molecular diversity enables PLAU to participate in both physiological and pathological processes in soluble and membrane-bound forms. Studies have shown that the conversion of pro-uPA to active uPA can occur not only in the extracellular space but also on the cell membrane, catalyzed by plasmin or other proteases. This spatially regulated activation is essential for maintaining tissue homeostasis.

The primary function of PLAU is to initiate the fibrinolytic cascade by converting plasminogen into plasmin. Under physiological conditions, PLAU works in concert with tissue-type plasminogen activator (tPA) to clear fibrin clots and maintain vascular patency. However, the role of PLAU extends far beyond fibrinolysis; it plays a broader part in the degradation and remodeling of the extracellular matrix (ECM). By binding to uPAR, PLAU becomes locally enriched at the leading edge of migrating cells, where it efficiently activates plasminogen. This, in turn, degrades various ECM components such as fibronectin, laminin, vitronectin, and type IV collagen. Such localized proteolytic activity provides a necessary "path-clearing" mechanism for cell migration, tissue repair, embryonic development, and angiogenesis. Furthermore, the PLAU-uPAR complex can mediate cell adhesion and signal transduction through integrin receptors, influencing cell proliferation, survival, and differentiation. During inflammatory responses, PLAU expression is induced by various cytokines (e.g., TGF-β, IL-1β, TNF-α), facilitating the infiltration of immune cells into inflammatory sites. Dysregulated expression or dysfunction of PLAU is closely associated with numerous human diseases, particularly malignancies, bleeding disorders, and neurodegenerative conditions.

Figure 1. Activation and Inhibition of the Fibrinolytic Pathway (Source: Kohler HP, et al. 2000)

Alternate Names for Plau

PLAU; plasminogen activator, urokinase; ATF; QPD; UPA; URK; u-PA; BDPLT5; urokinase-type plasminogen activator; U-plasminogen activator; plasminogen activator, urinary

• 1. Chen G, et al. PLAU Promotes Cell Proliferation and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma. Front Genet. 2021 May 20;12:651882.
  2. Kohler HP, et al. Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med. 2000 Jun 15;342(24):1792-801.