Molecular cloning and expression of human caldecrin

Tomomura, Akito; Akiyama, Masashi; Itoh, Hideomi; Yoshino, Izumi; Tomomura, Mineko; Nishii, Yasuho; Noikura, Takenori; Saheki, Takeyori

doi:10.1016/0014-5793(96)00377-8

Cited by 20 publications

(17 citation statements)

References 12 publications

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“…However, administration of procaldecrin did not decrease serum calcium levels [22] . Recombinant rat [11] and human [17] caldecrin also decreased serum calcium levels. In addition, rat protease activitydeficient caldecrin mutants (with His58Ala or Ser200Ala substitutions) decreased the levels of serum calcium.…”

Section: Activity Of Caldecrinmentioning

confidence: 89%

“…Caldecrin shows a greater similarity with elastase than with chymotrypsin. In addition, expressed recombinant human caldecrin also showed serum calcium-decreasing activity, even following phenylmethylsulfonyl fluoride treatment to abolish its protease activity [17] . In 1996, another research group purified a calcium metabolism-regulating factor from the porcine pancreas by determining its stimulatory effects on proliferation of the osteosarcoma MG-63 cell line and its inhibition of 1, 25 vitamin D3-stimulated calcium release in organ cultures [18] .…”

Section: Introductionmentioning

confidence: 98%

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Caldecrin: A pancreas-derived hypocalcemic factor, regulates osteoclast formation and function

Tomomura

2015

WJBC

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Caldecrin was originally isolated from the pancreas as a factor that reduced serum calcium levels. This secreted serine protease has chymotrypsin-like activity and is also known as chymotrypsin C; it belongs to the elastase family. Although intravenous administration of caldecrin decreases the serum calcium concentration even when its protease activity is blocked, this effect does require cleavage of caldecrin's pro-peptide by trypsin, converting it to the mature enzyme. Ectopic intramuscular expression of caldecrin prevented bone resorption in ovariectomized mice. Caldecrin inhibited parathyroid hormone-stimulated calcium release from fetal mouse long bone organ cultures. Furthermore, caldecrin suppressed the formation of osteoclasts from bone marrow cells by inhibiting the receptor activator of nuclear factor-k B ligand (RANKL)-stimulated phospholipase Cγ-calcium oscillation-calcineurinnuclear factor of activated T-cells, cytoplasmic 1 pathway. Caldecrin also suppressed the bone resorption activity of mature osteoclasts by preventing RANKL-stimulated Src activation, calcium entry, and actin ring formation. In vivo and in vitro studies have indicated that caldecrin is a unique multifunctional protease with anti-osteoclastogenic activities that are distinct from its protease activity. Caldecrin might be a potential therapeutic target for the treatment of osteolytic diseases such as osteoporosis and osteoarthritis. This mini-review describes caldecrin's historical background and its mechanisms of action. Core tip: Caldecrin (also known as chymotrypsin C) reduces serum calcium levels. This activity is distinct from its protease activity but also requires trypsin-mediated cleavage of the pro-peptide, converting caldecrin to its active form. Ectopic intramuscular expression of caldecrin prevented bone resorption in ovariectomized mice. Caldecrin inhibited parathyroid hormone-stimulated calcium release from fetal mouse long bones. Furthermore, caldecrin suppressed receptor activator of nuclear factor- MINIREVIEWS

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Section: Activity Of Caldecrinmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 98%

Caldecrin: A pancreas-derived hypocalcemic factor, regulates osteoclast formation and function

Tomomura

2015

WJBC

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“…Five of these were reported in 2013 by a genetic study from Japan; variants p.R29Q, p.S239A, p.S239C, and p.K247E were found in individuals with chronic pancreatitis, whereas variant p.I209M was detected in a control subject (15). Variant p.R80W was identified during the cDNA cloning of human CTRC, described then as a "serum calcium decreasing protein," caldecrin, by Japanese authors in 1996 (25). Two novel variants were also included in the present study; variant p.R80Q was found in a pancreatic cDNA sample, whereas variant p.G214R was discovered in a subject with chronic pancreatitis in Slovakia.…”

Section: Resultsmentioning

confidence: 99%

Mesotrypsin Signature Mutation in a Chymotrypsin C (CTRC) Variant Associated with Chronic Pancreatitis

Szabó

Ludwig

Hegyi

et al. 2015

Journal of Biological Chemistry

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“…Studies on cDNA of human and rat chymotrypsinogen C have revealed that their predicted sequences are rather conserved, comprising a signal peptide of 16 residues and a mature form of 252 residues that includes 10 cysteine residues [11,12]. The zymogen form is activated by trypsin and cleaved into a small and a large peptide fragment linked by a disulfide bond [2].…”

Section: Introductionmentioning

confidence: 99%

Purification, cDNA cloning, and recombinant expression of chymotrypsin C from porcine pancreas

Wang

Yuan

et al. 2011

ABBS

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Chymotrypsin C is a bifunctional secretory-type serine protease in pancreas; besides proteolytical activity, it also exhibits a calcium-decreasing activity in serum. In this study, we purified activated chymotrypsin C from porcine pancreas, and identified its three active forms. Active chymotrypsin C was found to be different in the length of its 13-residue activation peptide due to carboxydipeptidase ( present in the pancreas) degradation or autolysis of the activated chymotrypsin C itself, resulting in the removal of several C-terminus residues from the activation peptide. After limited chymotrypsin C cleavage with endopeptidase Lys C, several purified peptides were partially sequenced, and the entire cDNA sequence for porcine chymotrypsin C was cloned. Recombinant chymotrypsinogen C was successfully expressed in Escherichia coli cells as inclusion bodies. After refolding and activation with trypsin, the comparison of the recombinant chymotrypsin C with the natural form showed that their proteolytic and calcium-decreasing activities were at the same level. The successful expression of chymotrypsin C gene paves the way to further mutagenic structure2 function studies.

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Molecular cloning and expression of human caldecrin

Cited by 20 publications

References 12 publications

Caldecrin: A pancreas-derived hypocalcemic factor, regulates osteoclast formation and function

Caldecrin: A pancreas-derived hypocalcemic factor, regulates osteoclast formation and function

Mesotrypsin Signature Mutation in a Chymotrypsin C (CTRC) Variant Associated with Chronic Pancreatitis

Purification, cDNA cloning, and recombinant expression of chymotrypsin C from porcine pancreas

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