The Multiple Site Binding of Carboxypeptidase Y Inhibitor (IC) to the Cognate Proteinase

Mima, Joji; Narita, Yusuke; Chiba, Hayato

doi:10.1074/jbc.m301859200

Cited by 18 publications

(7 citation statements)

References 28 publications

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“…We have shown here that PEBP is present in bovine serum, although the protein has never been previously detected in human serum, lymph, or plasma probably because of low detection sensitivity (66). The quantification of PEBP present in blood was estimated to 35 nM, and this value fits well with the K i described for PEBPevoked carboxypeptidase-Y inhibition at 0.1 nM (60,61). In addition, because this peptide has been described to result from the activity of a granular chymotrypsin-like enzyme (10,44), it could also result from the activity of a circulating chymotrypsin-like enzyme after its secretion into the blood (67).…”

Section: Discussionsupporting

confidence: 70%

“…More recently, Parmer and colleagues (59) have shown that the plasmin-plasminogen system, which is present in the intragranular chromaffin matrix, seems to be implicated in chromogranin maturation. Interestingly, it has been reported that the yeast member of the PEBP family displays carboxypeptidase-Y inhibitor activity with a K i of 0.1 nM (60,61) and that mouse PEBP inhibits serine protease-like enzymes such as thrombin (K i ϭ 380 nM), chymotrypsin (K i ϭ 1.8 M), and neuropsin, but not plasmin, trypsin, and elastase (14). Taken together, these observations indicate that PEBP, as serpins (62), may modulate intragranular serine protease activities within chromaffin granules and thus control intragranular prohormone maturation.…”

Section: Discussionmentioning

confidence: 99%

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The Hippocampal Cholinergic Neurostimulating Peptide, the N-terminal Fragment of the Secreted Phosphatidylethanolamine-binding Protein, Possesses a New Biological Activity on Cardiac Physiology

Goumon

Angelone

Schoentgen

et al. 2004

Journal of Biological Chemistry

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Phosphatidylethanolamine-binding protein (PEBP), alternatively named Raf-1 kinase inhibitor protein, is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP) corresponding to its natural N-terminal fragment, previously described to be released by hippocampal neurons. PEBP is a soluble cytoplasmic protein, also associated with plasma and reticulum membranes of numerous cell types. In the present report, using biochemistry and cell biology techniques, we report for the first time the presence of PEBP in bovine chromaffin cell, a well described secretion model. We have examined its presence at the subcellular level and characterized this protein on both secretory granule membranes and intragranular matrix. In addition, its presence in bovine chromaffin cell and platelet exocytotic medium, as well as in serum, was reported showing that it is secreted. Like many other proteins that lack signal sequence, PEBP may be secreted through non-classic signal secretory mechanisms, which could be due to interactions with granule membrane lipids and lipid rafts. By two-dimensional liquid chromatography-tandem mass spectrometry, HCNP was detected among the intragranular matrix components. The observation that PEBP and HCNP were secreted with catecholamines into the circulation prompted us to investigate endocrine effects of this peptide on cardiovascular system. By using as bioassay an isolated and perfused frog (Rana esculenta) heart preparation, we show here that HCNP acts on the cardiac mechanical performance exerting a negative inotropism and counteracting the adrenergic stimulation of isoproterenol. All together, these data suggest that PEBP and HCNP might be considered as new endocrine factors involved in cardiac physiology.Chromaffin cells are derived from the neural crest and constitute the adrenal medulla. In the adrenal medullary chromaffin cell, secretory granules contain a complex mixture of proteins and peptides that are co-released with catecholamines into the circulation in response to splanchnic nerve stimulation (1) . Among the high molecular mass water-soluble proteins, proenkephalin-A and the chromogranins family constitute the major constituents of chromaffin granules with other neuropeptides (neuropeptide Y, vasointestinal peptide, and others). These proteins are actively processed in the intragranular matrix to peptides with various molecular weight (1-3). Recently, using highly sensitive proteomic techniques we have characterized the maturation products of proenkephalin-A (4) and established the presence of other unexpected proteins (5).Phosphatidylethanolamine-binding protein (PEBP) 1 (6, 7)/ Raf-1 kinase inhibitor protein (8) has previously been described in brain and adrenal gland (9, 10). PEBP is a 21-kDa protein initially described as a cytoplasmic protein and later found to be associated with plasma or reticulum membranes (11). This protein has been found in numerous tissues of many species, including rat testis, liver, kidney, and human platelets (6, 9, 10), indicating its ubi...

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

The Hippocampal Cholinergic Neurostimulating Peptide, the N-terminal Fragment of the Secreted Phosphatidylethanolamine-binding Protein, Possesses a New Biological Activity on Cardiac Physiology

Goumon

Angelone

Schoentgen

et al. 2004

Journal of Biological Chemistry

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“…This is a ubiquitous protein family that has been associated with serine protease inhibition [89], [90], although such activity has never been functionally characterized from any bloodsucking arthropod to date. Seven CDS were extracted from 815 reads deriving from the Am.…”

Section: Resultsmentioning

confidence: 99%

A Deep Insight into the Sialotranscriptome of the Gulf Coast Tick, Amblyomma maculatum

2011

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BackgroundSaliva of blood sucking arthropods contains compounds that antagonize their hosts' hemostasis, which include platelet aggregation, vasoconstriction and blood clotting; saliva of these organisms also has anti-inflammatory and immunomodullatory properties. Perhaps because hosts mount an active immune response against these compounds, the diversity of these compounds is large even among related blood sucking species. Because of these properties, saliva helps blood feeding as well as help the establishment of pathogens that can be transmitted during blood feeding.Methodology/Principal FindingsWe have obtained 1,626,969 reads by pyrosequencing a salivary gland cDNA library from adult females Amblyomma maculatum ticks at different times of feeding. Assembly of this data produced 72,441 sequences larger than 149 nucleotides from which 15,914 coding sequences were extracted. Of these, 5,353 had >75% coverage to their best match in the non-redundant database from the National Center for Biotechnology information, allowing for the deposition of 4,850 sequences to GenBank. The annotated data sets are available as hyperlinked spreadsheets. Putative secreted proteins were classified in 133 families, most of which have no known function.Conclusions/SignificanceThis data set of proteins constitutes a mining platform for novel pharmacologically active proteins and for uncovering vaccine targets against A. maculatum and the diseases they carry.

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“…It has also been reported that mCPY was specifically inhibited by I C , a proteinous proteinase inhibitor in the yeast S. cerevisiae. 13,15) Hence, to explore the similarity in inhibitory functions between the propeptide of proCPY and I C , amino acid sequence alignment between proCPY and I C was done (Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

Identification of Interaction Site of Propeptide toward Mature Carboxypeptidase Y (mCPY) Based on the Similarity between Propeptide and CPY Inhibitor (I^C)

Nagayama

Kuroda

Ueda

2012

Bioscience, Biotechnology, and Biochemistry

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The Multiple Site Binding of Carboxypeptidase Y Inhibitor (IC) to the Cognate Proteinase

Cited by 18 publications

References 28 publications

The Hippocampal Cholinergic Neurostimulating Peptide, the N-terminal Fragment of the Secreted Phosphatidylethanolamine-binding Protein, Possesses a New Biological Activity on Cardiac Physiology

The Hippocampal Cholinergic Neurostimulating Peptide, the N-terminal Fragment of the Secreted Phosphatidylethanolamine-binding Protein, Possesses a New Biological Activity on Cardiac Physiology

A Deep Insight into the Sialotranscriptome of the Gulf Coast Tick, Amblyomma maculatum

Identification of Interaction Site of Propeptide toward Mature Carboxypeptidase Y (mCPY) Based on the Similarity between Propeptide and CPY Inhibitor (I^C)

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The Multiple Site Binding of Carboxypeptidase Y Inhibitor (IC) to the Cognate Proteinase

Cited by 18 publications

References 28 publications

The Hippocampal Cholinergic Neurostimulating Peptide, the N-terminal Fragment of the Secreted Phosphatidylethanolamine-binding Protein, Possesses a New Biological Activity on Cardiac Physiology

The Hippocampal Cholinergic Neurostimulating Peptide, the N-terminal Fragment of the Secreted Phosphatidylethanolamine-binding Protein, Possesses a New Biological Activity on Cardiac Physiology

A Deep Insight into the Sialotranscriptome of the Gulf Coast Tick, Amblyomma maculatum

Identification of Interaction Site of Propeptide toward Mature Carboxypeptidase Y (mCPY) Based on the Similarity between Propeptide and CPY Inhibitor (IC)

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Identification of Interaction Site of Propeptide toward Mature Carboxypeptidase Y (mCPY) Based on the Similarity between Propeptide and CPY Inhibitor (I^C)