Proteolysis of ProPTHrP(1–141) by “Prohormone Thiol Protease” at Multibasic Residues Generates PTHrP-Related Peptides: Implications for PTHrP Peptide Production in Lung Cancer Cells

Hook, Vivian; Burton, Douglas W.; Yasothornsrikul, Sukkid; Hastings, Randolph H.; Deftos, Leonard J.

doi:10.1006/bbrc.2001.5249

Cited by 26 publications

(13 citation statements)

References 27 publications

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“…Several bioactive peptides can exert more than one physiological effect in the human body (Erdmann et al 2008), and some of these include : antihypertensive, immunomodulating, anti-thrombotic, antioxidative, opioid, cholesterol lowering, anticancer, and antimicrobial activities (Vercruysse et al 2005). The peptides exhibited several bioactivities like inhibition of lipid peroxidation and elimination of free radicals produced in vivo and the activity depends on their amino acid composition and sequences (Hook et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Optimization of enzymatic hydrolysis conditions for the production of antioxidant peptides from muscles of Nemipterus japonicus and Exocoetus volitans using response surface methodology

Naqash

Nazeer

2011

Amino Acids

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In the present study, protein of muscles of commercially important marine fishes Nemipterus japonicus and Exocoetus volitans were extracted by trypsin and their hydrolysis conditions viz., temperature, time, and enzyme to substrate concentration on degree of hydrolysis were studied by response surface methodology. The optimum values for N. japonicus was found as temperature, 30°C, hydrolysis time of 100 min an enzyme/substrate concentration of 1.59% whereas, for E. volitans muscle protein, optimum hydrolysis conditions were temperature, 30°C, hydrolysis time of 115 min and enzyme/substrate concentration of 1.67%. Furthermore, amino acid sequence of antioxidant peptides derived after chromatographic purification was identified by ESI-MS/MS. The analysis of peptides showed sequences as Glu-Ser-Asp-Arg-Pro (620.3 Da) and Gly-Trp-Met-Gly-Cys-Trp (747.3) for N. japonicus and E. volitans muscle, respectively. The peptides contained important antioxidant amino acids and acted as good antioxidant peptides to scavenge free radicals.

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Section: Introductionmentioning

confidence: 99%

Optimization of enzymatic hydrolysis conditions for the production of antioxidant peptides from muscles of Nemipterus japonicus and Exocoetus volitans using response surface methodology

Naqash

Nazeer

2011

Amino Acids

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“…Interestingly, the locally generated PTHrP was shown to be subsequently involved in regulating cell growth. Furthermore, lung cancer cell lines that express low levels of PTHrP were found not to express PTP [57]. These studies suggest that depending on the tissue context, multiple proteases can contribute to generating PTHrP1–36 and other PTHrP products.…”

Section: Proteolytic Control Of Pthrp Functionmentioning

confidence: 99%

“…The presence of multiple predicted mono- and multi-basic cleavage sites within the PTHrP protein sequence indicates that it is likely susceptible to proteolytic cleavage [55]. Indeed removal of the leader sequence and cleavage at Arg37 by enzymes such as furin or prothiol hormone protease have been reported to generate PTHrP1–36 [56,57], therefore, it is possible that additional functions for PTHrP products outside of those known for PTHrP1–36 in bone or other tissues remain to be identified. Growing evidence indicates that subsequent to removal of the leader sequence (-36 to -1), the protein remains subject to further modification by proteolytic cleavage [18].…”

Section: Introductionmentioning

confidence: 99%

Proteolytic Regulation of Parathyroid Hormone-Related Protein: Functional Implications for Skeletal Malignancy

Frieling

Lynch

2019

IJMS

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Parathyroid hormone-related protein (PTHrP), with isoforms ranging from 139 to 173 amino acids, has long been implicated in the development and regulation of multiple tissues, including that of the skeleton, via paracrine and autocrine signaling. PTHrP is also known as a potent mediator of cancer-induced bone disease, contributing to a vicious cycle between tumor cells and the bone microenvironment that drives the formation and progression of metastatic lesions. The abundance of roles ascribed to PTHrP have largely been attributed to the N-terminal 1–36 amino acid region, however, activities for mid-region and C-terminal products as well as additional shorter N-terminal species have also been described. Studies of the protein sequence have indicated that PTHrP is susceptible to post-translational proteolytic cleavage by multiple classes of proteases with emerging evidence pointing to novel functional roles for these PTHrP products in regulating cell behavior in homeostatic and pathological contexts. As a consequence, PTHrP products are also being explored as potential biomarkers of disease. Taken together, our enhanced understanding of the post-translational regulation of PTHrP bioactivity could assist in developing new therapeutic approaches that can effectively treat skeletal malignancies.

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“…This duality of secretory mechanisms indicates that PTHrP is unusual with respect to other precursors in that it is both a neuroendocrine peptide and a growth factor or cytokine. During its transit through the secretory pathway, the precursor is endoproteolytically processed at basic residues to yield a family of mature secretory forms of the peptide [80]. PTHrP(1–36), displays smooth muscle relaxant properties and growth factor effects similar to PTHrP; PTHrP(38–94/95/101) regulates calcium transport; PTHrP(107–139), known as osteostatin, modulates osteoclast activity; and PTHrP(141–173) stimulates the growth of bone cells and collagen synthesis.…”

Section: Pth‐related Proteinmentioning

confidence: 99%

Biologically active, non membrane‐anchored precursors – an overview

Dicou

2008

The FEBS Journal

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Peptides function as chemical signals between cells of multicellular organisms via specific receptors on target cells. Many hormones, neuromodulators and growth factors are peptides. Peptide hormones and other biologically active peptides are synthesized as higher molecular weight precursor proteins (pro‐hormones), which must undergo post‐translational modification to yield the bioactive peptide(s). In many instances, more than one biologically active peptide is generated from one and the same precursor. In most cases, these precursors are biologically inert and their existence is confined to the membrane‐enclosed subcellular compartments where processing of the pro‐hormones takes place. A class of growth factors that derive from membrane‐anchored precursors which themselves are biologically active constitute an exception to this model. The list of the membrane‐anchored biologically active precursors has been the subject of specialized reviews. The present review focuses on precursors other than membrane‐anchored precursors, which were found to be biologically active and which often display different biological activities, and may mediate their effects via receptors independent from those of their generated peptides.

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Proteolysis of ProPTHrP(1–141) by “Prohormone Thiol Protease” at Multibasic Residues Generates PTHrP-Related Peptides: Implications for PTHrP Peptide Production in Lung Cancer Cells

Cited by 26 publications

References 27 publications

Optimization of enzymatic hydrolysis conditions for the production of antioxidant peptides from muscles of Nemipterus japonicus and Exocoetus volitans using response surface methodology

Optimization of enzymatic hydrolysis conditions for the production of antioxidant peptides from muscles of Nemipterus japonicus and Exocoetus volitans using response surface methodology

Proteolytic Regulation of Parathyroid Hormone-Related Protein: Functional Implications for Skeletal Malignancy

Biologically active, non membrane‐anchored precursors – an overview

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