Isolation and Characterization of the Plasma Hyaluronan-Binding Protein (PHBP) Gene (HABP2)

Sumiya, Jun-ichi; Asakawa, Shuichi; Tobe, Takashi; Hashimoto, Ken; Saguchi, Ken-ichi; Choi-Miura, Nam-Ho; Shimizu, Yoshiko; Minoshima, Shinsei; Shimizu, Nobuyoshi; Tomita, Motowo

doi:10.1093/oxfordjournals.jbchem.a021861

Cited by 39 publications

(36 citation statements)

References 32 publications

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“…A human protein similar to HGFA has recently been identified (22,23) (GenBank TM accession number AAB46909). This molecule, hyaluronin-binding protein, was only 38% identical to murine HGFA at the amino acid level.…”

Section: Resultsmentioning

confidence: 99%

“…However, other members of the plasminogen activator family, coagulation factor XII, tissue plasminogen activator (tPA), and urokinase (uPA), are also weak activators of HGF (11,15,16). An HGFAlike molecule, PHBP, has recently been identified and could potentially, based on its sequence, activate HGF (22,23). Two of these enzymes, tPA and uPA, are also expressed in developing kidney (29).…”

Section: Figmentioning

confidence: 99%

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Activation of Hepatocyte Growth Factor (HGF) by Endogenous HGF Activator Is Required for Metanephric Kidney Morphogenesis in Vitro

Adelsberg

Sehgal

Kukes

et al. 2001

Journal of Biological Chemistry

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The interaction of hepatocyte growth factor (HGF) with c-Met has been implicated in morphogenesis of the kidney, lung, mammary gland, liver, placenta, and limb bud. HGF is secreted as an inactive zymogen and must be cleaved by a serine protease to initiate Met signaling. We show here that a serine protease specific for HGF, HGF activator (HGFA), is expressed and activated by the ureteric bud of the developing kidney in vivo and in vitro. Inhibition of HGFA activity with serine protease inhibitors reduced ureteric bud branching and inhibited glomerulogenesis and nephrogenesis. Activated HGF rescued developing kidneys from the effects of inhibitors. HGFA was localized around the tips of the ureteric bud in developing kidneys, while HGF was expressed diffusely throughout the mesenchyme. These data show that expression of HGF is not sufficient for development, but that its activation is also required. The localization of HGFA to the ureteric bud and the mesenchyme immediately adjacent to it suggests that HGFA creates a gradient of HGF activity in the developing kidney. The creation and shape of gradients of activated HGF by the localized secretion of HGF activators could play an important role in pattern formation by HGF responsive tissues.

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Section: Resultsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Activation of Hepatocyte Growth Factor (HGF) by Endogenous HGF Activator Is Required for Metanephric Kidney Morphogenesis in Vitro

Adelsberg

Sehgal

Kukes

et al. 2001

Journal of Biological Chemistry

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“…In the remaining population, follow-up was 96.5% (nϭ826) and 95.6% (nϭ684) complete, respectively. [1][2][3] Blood specimens for DNA extraction were drawn as part of the 1995 follow-up. Adequate polymerase chain reaction products were not obtainable in 16 samples, which left 810 (1995) and 678 (2000) subjects for the main analysis.…”

Section: Study Subjectsmentioning

confidence: 99%

“…The plasmatic serine protease factor seven-activating protease (FSAP) has been recognized as a novel potent activator of prourokinase-dependent fibrinolysis. [1][2][3][4][5][6] We recently characterized a single nucleotide polymorphism (SNP) of FSAP, termed "Marburg I polymorphism," which impairs the capacity of FSAP to activate prourokinase without attenuating its potential contribution to the extrinsic coagulation pathway. 4 -6 This may drive hemostasis toward a prothrombotic state.…”

mentioning

confidence: 99%

Marburg I Polymorphism of Factor VII–Activating Protease

Willeit¹,

Kiechl²,

Weimer³

et al. 2003

Circulation

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Background-Atherothrombosis is a main pathomechanism in the evolution of vessel stenosis and is counteracted by endogenous fibrinolysis. Recently, the plasmatic serine protease "factor seven-activating protease" (FSAP) was recognized as a potent activator of prourokinase in vitro. The Marburg I polymorphism of FSAP impairs this potential and may thus facilitate arterial thrombosis. Methods and Results-This analysis of the Bruneck Study involved 810 men and women aged 40 to 79 years. The ultrasound-based atherosclerosis progression model (5-year follow-up) permits differentiation between early atherogenesis and the advanced stenotic stages of carotid artery disease. The FSAP Marburg I polymorphism was found in 37 subjects (carriage rate 4.4%). Individuals with this genetic variant showed a prominently reduced in vitro capacity to activate prourokinase. No relation was found to exist between the Marburg I polymorphism and early atherogenesis. In contrast, it emerged as a strong and independent risk predictor of incident/progressive carotid stenosis (multivariate odds ratio [95%CI], 6.6 [1.6 to 27.7]). This finding equally applied to subjects with and without co-segregation of the Marburg II polymorphism. The risk profile of advanced atherogenesis further includes cigarette smoking, high lipoprotein(a), the factor V Leiden mutation, low antithrombin III, high fibrinogen, and diabetes. Conclusions-In concert with other genetic and acquired conditions known to interfere with coagulation or fibrinolysis, the Marburg I polymorphism of FSAP, which attenuates its capacity to activate prourokinase, is a significant risk predictor for the evolution and progression of carotid stenosis.

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“…Single-chain PHBP is a 70-kDa zymogen that exists in human plasma at a concentration of 12 μg/ml and can be cleaved autocatalytically to generate the active two-chain form (50 kDa and 27 kDa) linked by a disulfide bond (13,14). PHBP exhibits a strong affinity for negatively charged substances such as hyaluronic acid, dextran sulfate, or heparin, all of which enhance autoactivation.…”

Section: Introductionmentioning

confidence: 99%

Anti-angiogenic action of plasma hyaluronan binding protein in human umbilical vein endothelial cells

Jeon

Song²,

Moon³

et al. 2006

Int J Oncol

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Abstract.The kringle domain is a triple loop structure present in angiostatin and endostatin. The disulfide bond-linked kringle architectures have been known to be essential for anti-angiogenic activity. Plasma hyaluronan binding protein (PHBP) is a novel serine protease which consists of three epidermal growth factor (EGF) domains, a kringle domain, and a serine protease domain. PHBP can be cleaved autocatalytically to generate activity and is highly expressed in the human blood and liver. To determine the anti-angiogenic activities of PHBP, we purified recombinant mouse PHBP from stable cell line overexpressing PHBP and used protein in vivo and in vitro angiogenesis assays. We found that recombinant PHBP inhibits not only angiogenesis in vivo in chorioallantoic membrane (CAM) assay but also the basic fibroblast growth factor (bFGF)-induced proliferation, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependant manner. Moreover, we found that the kringle domain of PHBP was essential for the antiangiogenic action of PHBP by the deletion mutants. These findings unravel a new function of PHBP as an inhibitor of the proangiogenic phenotype of vascular endothelial cells and demonstrate that the kringle domain of PHBP might be a potent novel inhibitor of activated endothelial cells in vitro and in vivo.

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Isolation and Characterization of the Plasma Hyaluronan-Binding Protein (PHBP) Gene (HABP2)

Cited by 39 publications

References 32 publications

Activation of Hepatocyte Growth Factor (HGF) by Endogenous HGF Activator Is Required for Metanephric Kidney Morphogenesis in Vitro

Activation of Hepatocyte Growth Factor (HGF) by Endogenous HGF Activator Is Required for Metanephric Kidney Morphogenesis in Vitro

Marburg I Polymorphism of Factor VII–Activating Protease

Anti-angiogenic action of plasma hyaluronan binding protein in human umbilical vein endothelial cells

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