Primary structure of single-chain pro-urokinase.

Kasai, S; Arimura, Hirofumi; Nishida, Masayuki; Suyama, Takehiro

doi:10.1016/s0021-9258(17)39036-1

Cited by 88 publications

(10 citation statements)

References 18 publications

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“…Pro-uPA is a glycoprotein containing 411 amino acids with 24 cysteine, 22 arginine and 27 lysine residues (28). N-glycosylation of human uPA occurs at Asn302 in the protease domain (30). The N-glycans of uPA contain Man, Gal, Fuc, GlcNAc and NeuSAc, as well as GalNAc residues (31).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the correlation between alterations in N‑glycans and invasiveness in liver cancer cell lines

et al. 2020

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The N-glycoforms of glycoproteins modify protein function and control a number of biological pathways. The aim of the present study was to investigate the correlation between alterations in N-glycans and cancer aggressiveness in terms of cancer cell invasion ability. The expression of urokinase-type plasminogen activator (uPA) and N-acetylglucosaminyltr ansferase V (GnT-V) in liver cancer cell lines was analyzed by western blotting. Cell invasiveness was analyzed by Matrigel invasion assays. uPA and GnT-V expression in liver cancer cell lines was knocked down by RNA interference. Furthermore, uPA was overexpressed in liver cancer cells using lentiviral vectors, and a mutant strain of HepG2 cells overexpressing uPA deficient in N-glycans was established. A glycoblotting-assisted matrix-assisted laser desorption/ionization-time-of-flight/mass spectrometry-based quantitative analysis of liver cancer cell lines was performed, in which invasiveness was altered by modifying the expression of uPA and GnT-V. N-glycan profiles were found to differ between the highly invasive liver cancer cell line HLE and the less invasive cell line HepG2. The expression of several N-glycans, including a form with m/z=1892, was changed according to invasiveness controlled by knockdown and overexpression of uPA. The invasiveness of HepG2 cells with mutant uPA did not increase regardless of the level of expression of uPA. Following GnT-V knockdown and N-glycan alteration, uPA expression did not change, whereas cell invasiveness decreased. One N-glycan (m/z=1892) was common among N-glycans in the comparative analysis between HLE and HepG2, HLE and uPA knockdown HLE, HepG2 and uPA-overexpressing HepG2, and HLE and GnT-V knockdown HLE cells and among N-glycan profiles in human uPA. Therefore, N-glycosylation is an important factor controlling invasiveness of liver cancer cells, and a specific N-glycan (m/z=1892) associated with the invasion of liver cancer cells via uPA was identified in the present study.

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Section: Discussionmentioning

confidence: 99%

Analysis of the correlation between alterations in N‑glycans and invasiveness in liver cancer cell lines

et al. 2020

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“…Regions comprising the S1 specificity pocket and oxyanion hole are displaced in single-chain pro-uPA, leading to disruption of this salt bridge and explaining its low proteolytic activity (Hedstrom 2002). Cleavage of the Lys158-Ile159 bond by plasmin generates the active, disulfide-linked two-chain high molecular weight (HMW; residues 1-411) uPA (Kasai et al 1985;Magill et al 1999;Spraggon et al 1995). Further cleavage of the Lys135-Ile136 bond in chain A yields soluble, low molecular weight (LMW; residues 136-411) uPA and an amino-terminal fragment (ATF; residues 1-135) (Stepanova & Tkachuk 2002).…”

Section: Structure Of Upamentioning

confidence: 99%

Urokinase plasminogen activator as an anti-metastasis target: inhibitor design principles, recent amiloride derivatives, and issues with human/mouse species selectivity

et al. 2022

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“…Like tPA, uPA is found in the plasma at approximately the same concentration of 5-10 µg/L, but it is produced by cells in the lungs, kidneys as well as keratinocytes and endothelial cells. The uPA is synthesized as a 55 kDa single-chain protein consisting of 411 amino acids [102]. This multidomain protein has an EGF-like domain, one kringle domain, and a serine protease domain.…”

Section: Plasminogen Activatorsmentioning

confidence: 99%

Plasmin and Plasminogen System in the Tumor Microenvironment: Implications for Cancer Diagnosis, Prognosis, and Therapy

Bharadwaj

Holloway

Miller

et al. 2021

Cancers

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The tumor microenvironment (TME) is now being widely accepted as the key contributor to a range of processes involved in cancer progression from tumor growth to metastasis and chemoresistance. The extracellular matrix (ECM) and the proteases that mediate the remodeling of the ECM form an integral part of the TME. Plasmin is a broad-spectrum, highly potent, serine protease whose activation from its precursor plasminogen is tightly regulated by the activators (uPA, uPAR, and tPA), the inhibitors (PAI-1, PAI-2), and plasminogen receptors. Collectively, this system is called the plasminogen activation system. The expression of the components of the plasminogen activation system by malignant cells and the surrounding stromal cells modulates the TME resulting in sustained cancer progression signals. In this review, we provide a detailed discussion of the roles of plasminogen activation system in tumor growth, invasion, metastasis, and chemoresistance with specific emphasis on their role in the TME. We particularly review the recent highlights of the plasminogen receptor S100A10 (p11), which is a pivotal component of the plasminogen activation system.

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Primary structure of single-chain pro-urokinase.

Cited by 88 publications

References 18 publications

Analysis of the correlation between alterations in N‑glycans and invasiveness in liver cancer cell lines

Analysis of the correlation between alterations in N‑glycans and invasiveness in liver cancer cell lines

Urokinase plasminogen activator as an anti-metastasis target: inhibitor design principles, recent amiloride derivatives, and issues with human/mouse species selectivity

Plasmin and Plasminogen System in the Tumor Microenvironment: Implications for Cancer Diagnosis, Prognosis, and Therapy

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