Roles of CUB and LDL receptor class A domain repeats of a transmembrane serine protease matriptase in its zymogen activation
JOURNAL OF BIOCHEMISTRY
Authors: Inouye, Kuniyo; Tomoishi, Marie; Yasumoto, Makoto; Miyake, Yuka; Kojima, Kenji; Tsuzuki, Satoshi; Fushiki, Tohru
Abstract
Matriptase is a type II transmembrane serine protease containing two complement proteases C1r/C1s-urchin embryonic growth factor-bone morphogenetic protein domains (CUB repeat) and four low-density lipoprotein receptor class A domains (LDLRA repeat). The single-chain zymogen of matriptase has been found to exhibit substantial protease activity, possibly causing its own activation (i.e. conversion to a disulfide-linked two-chain fully active form), although the activation seems to be mediated predominantly by two-chain molecules. Our aim was to assess the roles of CUB and LDLRA repeats in zymogen activation. Transient expression studies of soluble truncated constructs of recombinant matriptase in COS-1 cells showed that the CUB repeat had an inhibitory effect on zymogen activation, possibly because it facilitated the interaction of two-chain molecules with a matriptase inhibitor, hepatocyte growth factor activator inhibitor type-1. By contrast, the LDLRA repeat had a promoting effect on zymogen activation. The effect of the LDLRA repeat seems to reflect its ability to increase zymogen activity. The proteolytic activities were higher in pseudozymogen forms of recombinant matriptase containing the LDLRA repeat than in a pseudozymogen without the repeat. Our findings provide new insights into the roles of these non-catalytic domains in the generation of active matriptase.
A new biomarker for the early diagnosis of ovarian torsion: SCUBE-1
CLINICAL AND EXPERIMENTAL REPRODUCTIVE MEDICINE-CERM
Authors: Uyanikoglu, Hacer; Hilali, Nese Gul; Yardimciel, Mesut; Koyuncu, Ismail
Abstract
Objective: Prompt diagnosis and management are essential for saving the adnexal organs from infarction in cases of ovarian torsion (OT). This study aimed to determine the diagnostic significance of signal peptide, complement C1r/C1s, Uegf, and Bmp1 (CUB), and epidermal growth factor-like domain-containing protein-1 (SCUBE-1) levels in cases of OT, an emergent ischemic condition, and the relationship of SCUBE-1 with oxidative stress parameters. Methods: This prospective study was conducted among 15 OT patients and 20 age-and gravidity-matched healthy women. SCUBE-1 serum concentrations were determined by using enzyme-linked immunosorbent assays. In addition, oxidative stress was evaluated by measuring the serum levels of advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP), and glutathione (GSH). Results: The SCUBE-1 titers were significantly higher in the patients with OT than in the controls (p = 0.008). In addition, serum FRAP and GSH levels were significantly lower in the OT patients than in the controls (p< 0.001 for both). Serum AOPP levels were higher in the OT patients, but this trend was not statistically significant (p> 0.05). Furthermore, there were no correlations between SCUBE-1 levels and age, gravidity, parity, cyst size, and AOPP, FRAP, or GSH levels (p> 0.05). Conclusion: We believe that SCUBE-1 may be a promising biomarker for the early diagnosis of OT.