cDNA and deduced amino acid sequence of human PK‐120, a plasma kallikrein‐sensitive glycoprotein

Nishimura, Hitoshi; Kakizaki, Ikuko; Muta, Tsuyoshi; Sasaki, Naosuke; Pu, Ping Xiao; Yamashita, Toshiyuki; Nagasawa, Shigeharu

doi:10.1016/0014-5793(94)01364-7

Cited by 68 publications

(11 citation statements)

References 16 publications

(7 reference statements)

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“…On the basis of expression studies, ITIH4 is primarily synthesized in the liver, 1 and four isoforms of ITIH4 have been predicted based on mRNA and/or cDNA sequencing experiments. 12,58,59 Three ITIH4 isoforms have been described in adult liver tissue, while the fourth was found in fetal human liver. Isoform 1 was the first to be described and has been selected as the “canonical” sequence in UniProt.…”

Section: Discussionmentioning

confidence: 99%

“…7−11 ITIH4 can be cleaved by plasma kallikrein into two fragments that undergo additional proteolytic processing into an 85 kDa N-terminal fragment and a 35 kDa C-terminal fragment. 12−14 The plasma kallikrein cleavage site is found within the proline-rich region (PRR) of ITIH4. ITIH4 also contains a von Willebrand factor A (vWF) domain, which may mediate interactions with other proteins.…”

Section: Introductionmentioning

confidence: 99%

“…12,14 ITIH4 is N-glycosylated at N81, N207, N517, and N577, 28−31 and there is also evidence that ITIH4 is O-glycosylated within the PRR and near the plasma kallikrein cleavage site. 12,32 Characterization of ITIH4 glycoforms may aid in determining if ITIH4 stability is affected by glycosylation, offer clues about its role in extracellular matrix stability and as an acute phase protein, and offer insight into potential interactions of ITIH4 with glycan binding proteins involved in inflammation and adhesion. Previous reports indicate that all four canonical N-glycosylation sites (N-X-S/T) of ITIH4 are glycosylated in human serum, but site occupancy and microheterogeneity of its glycoforms remain undefined.…”

Section: Introductionmentioning

confidence: 99%

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Site-Specific Glycan Microheterogeneity of Inter-Alpha-Trypsin Inhibitor Heavy Chain H4

et al. 2014

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Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is a 120 kDa acute-phase glycoprotein produced primarily in the liver, secreted into the blood, and identified in serum. ITIH4 is involved in liver development and stabilization of the extracellular matrix (ECM), and its expression is altered in liver disease. In this study, we aimed to characterize glycosylation of recombinant and serum-derived ITIH4 using analytical mass spectrometry. Recombinant ITIH4 was analyzed to optimize glycopeptide analyses, followed by serum-derived ITIH4. First, we confirmed that the four ITIH4 N-X-S/T sequons (N81, N207, N517, and N577) were glycosylated by treating ITIH4 tryptic/GluC glycopeptides with PNGaseF in the presence of 18O water. Next, we performed glycosidase-assisted LC–MS/MS analysis of ITIH4 trypsin-GluC glycopeptides enriched via hydrophilic interaction liquid chromatography to characterize ITIH4 N-glycoforms. While microheterogeneity of N-glycoforms differed between ITIH4 protein expressed in HEK293 cells and protein isolated from serum, occupancy of N-glycosylation sites did not differ. A fifth N-glycosylation site was discovered at N274 with the rare nonconsensus NVV motif. Site N274 contained high-mannose N-linked glycans in both serum and recombinant ITIH4. We also identified isoform-specific ITIH4 O-glycoforms and documented that utilization of O-glycosylation sites on ITIH4 differed between the cell line and serum.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Site-Specific Glycan Microheterogeneity of Inter-Alpha-Trypsin Inhibitor Heavy Chain H4

et al. 2014

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“…It is the only member of the ITI family which harbours a kallikrein-released bradykinin-like domain in its C-terminal sequence [3], making it plasma kallikrein sensitive [4-6]. Trace amounts of plasma kallikrein have been shown to cleave ITIH4 to yield two fragments, i.e., a 35 kDa C-terminal polypeptide and an 85 kDa N-terminal fragment [7].…”

Section: Introductionmentioning

confidence: 99%

“…Trace amounts of plasma kallikrein have been shown to cleave ITIH4 to yield two fragments, i.e., a 35 kDa C-terminal polypeptide and an 85 kDa N-terminal fragment [7]. The 35 kDa ITIH4 fragment, which is O -glycosylated [3,8], is assumed to remain intact. However, the 85 kDa ITIH4 fragment is further cleaved to produce an N-terminal 57 kDa fragment and a putative 28 kDa fragment.…”

Section: Introductionmentioning

confidence: 99%

Enhanced expression of a 35 kDa fragment of inter-alpha-trypsin inhibitor H4 in sera of healthy pregnant women and patients with hydatidiform mole

et al. 2013

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BackgroundAccumulated data from previous studies appear to suggest a link between the overexpression of a 35 kDa fragment of serum inter-alpha-trypsin inhibitor H4 (ITIH4) with cancers that are associated with up-regulated levels of oestrogens. The truncated fragment was postulated to be a product of oestrogen-induced action of kallikrein on native ITIH4. The present lectin-based proteomic analyses were performed to assess the specificity of the 35 kDa fragment of ITIH4 as a potential cancer biomarker and determine whether it was also overexpressed in the sera of cancer-negative pregnant women who are known to have high levels of plasma oestrogens.ResultsOur results demonstrated that the 35 kDa fragment of ITIH4 was overexpressed in healthy pregnant women and patients with hydatidiform mole, relative to the controls. The serum oestradiol levels of both groups of pregnant subjects were also confirmed to be higher than those of the control women who were not pregnant.ConclusionsOverexpression of the 35 kDa fragment of ITIH4 was not restrictive to patients with cancers but also occurred in women who were pregnant and those diagnosed with hydatidiform mole. Our data implicate the limitation of the 35 kDa ITIH4 fragment as a cancer biomarker and its correlation with serum oestrogen levels.

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Analysis of plasma protein adsorption on polymeric nanoparticles with different surface characteristics

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Paulke

Schröder

et al. 1998

J. Biomed. Mater. Res.

210

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Plasma protein adsorption patterns on colloidal drug carriers acquired after i.v. administration depend on their surface characteristics and are regarded as key factors for their in vivo organ distribution. Polymeric latex particles with strongly differing surface properties were synthesized as models for colloidal drug carriers for tissue-specific drug targeting via the intravenous route. Physicochemical characterization was performed for size, surface charge density, zeta potential, and surface hydrophobicity. The interactions with human plasma proteins were studied by way of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Considerable differences in protein adsorption on the latex particles were detected with regard to the total amount of surface-bound protein on the various particle types as well as specific proteins adsorbed, for example, fibrinogen, albumin, and a recently identified plasma glycoprotein. Possible correlations between protein adsorption patterns and the physicochemical characteristics and topography of the polymeric surfaces are shown and discussed. Knowledge about protein-nanoparticle interactions can be utilized for the rational design of colloidal drug carriers and also may be useful for optimizing implants and medical devices.

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cDNA and deduced amino acid sequence of human PK‐120, a plasma kallikrein‐sensitive glycoprotein

Cited by 68 publications

References 16 publications

Site-Specific Glycan Microheterogeneity of Inter-Alpha-Trypsin Inhibitor Heavy Chain H4

Site-Specific Glycan Microheterogeneity of Inter-Alpha-Trypsin Inhibitor Heavy Chain H4

Enhanced expression of a 35 kDa fragment of inter-alpha-trypsin inhibitor H4 in sera of healthy pregnant women and patients with hydatidiform mole

Analysis of plasma protein adsorption on polymeric nanoparticles with different surface characteristics

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