Purification and Characterization of Porcine Corticotrophin-Like Intermediate Lobe Peptide

Scott, A. P.; Lowry, P. J.; Bennett, H. P. J.; McMartin, Colin; Ratcliffe, John G.

doi:10.1677/joe.0.0610369

Cited by 51 publications

(11 citation statements)

References 14 publications

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“…1). The precursor hypothesis of Scott et al (132) was finally confirmed in our laboratory by pulse-chase experiments (133). It is not yet proven if CLIP is cleaved as a separate entity (133) in large amounts.…”

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confidence: 75%

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Chemistry and biosynthesis of pro-opiomelanocortin

Chrétien

Seidah

1981

Mol Cell Biochem

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Studies of lipotropins, melanotropins and endorphins on one hand, and of adrenocorticotropin on the other, has given rise to the concept of a multipotent precursor molecule recently renamed proopiomelanocortin. The preferential sites of cleavage of the precursor to produce its biologically active components are made of pairs of basic amino acid residues as described for the biosynthesis of beta-MSH and pro-insulin. Such structural feature is also found in other pro-hormone molecules. Pulse chase experiments and secretory studies carried out in both anterior and intermediate lobes of rat pituitary glands revealed the transformation of different forms of the precursor into different end-products, the anterior lobe producing preferentially ACTH and beta-LPH while the intermediate produces mainly the alpha-MSH and beta-endorphin. The multiple forms of precursors seem to differ in their carbohydrate content although at least two different gene products are still possible. The presence of similar peptides in the hypothalamus makes it highly probable that neuropeptides are biosynthesized with similar process. Thus the model of beta-LPH precursor, proposed as early as in 1967, is now applicable to the biosynthesis of all other neuropeptides. Major advances in this field are expected in the 1980s.

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confidence: 75%

“…It was later sequenced and found to consist of residues 18-39 of ACTH (132). This finding, based on structure analysis, led these authors to conclude that ACTH was the precursor of both alpha-MSH and CLIP.…”

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confidence: 99%

Chemistry and biosynthesis of pro-opiomelanocortin

Chrétien

Seidah

1981

Mol Cell Biochem

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“…was processed by proteolytic cleavage to other peptides with lower molecular weights such as ct-MSH (ACTH 1.13) and CLIP (ACTH|g_39) [13,17,34,35]. The interme diate lobe contained little ACTH|_39 [8,17] but a lot of a-MSH, CLIP and (3-endorphin [6,17,22,26,30,42,43], In the anterior lobe, ACTH|_39 and p-LPH were terminal products resulting from proteolytic cleavage of a common precursor, pro-opiomclanocortin [23,29,30], In the hypothalamus of young female rats the evolution of peptides related to (3-endorphin was similar to that of pituitary ACTH. From day 14 to 20 after birth, the elution peak of P-LPH decreased whereas that of p-endorphin increased by 50% [20],…”

Section: Discussionmentioning

confidence: 99%

Adrenocorticotrophic Hormone in the Anterior and Neurointermediate Lobes of the Rat during the Perinatal Period: Polymorphism, Biological and Immunological Activities of ACTH

Chatelain¹,

Dupouy²

1985

Neonatology

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When acid extracts (0.1 NHCl) of the anterior or neurointermediate lobes of fetal and newborn rat pituitary were subjected to gel filtration on Sephadex G-50 fine columns, polymorphism of ACTH was revealed by radioimmunoassay. At every stage of pregnancy and after birth three main ACTH forms were observed. The first form (‘big’ ACTH) eluted near the void volume of the column; its apparent molecular weight was 45,000. The second form (‘little’ ACTH) coeluted with synthetic human ACTH_1–39 and ¹²⁵I human ACTH. As the latter marker eluted more slowly than the former, ‘little’ ACTH, which showed an apparent molecular weight near 5,000, could not be a single entity. The third form (‘intermediate’ ACTH) eluted between ‘big’ and ‘little’ ACTH; its apparent molecular weight was near 13,000. During the perinatal period, the relative proportions between these different molecular forms of ACTH changed in both anterior and neurointermediate lobes. Thus the gradual increase of ‘intermediate’ and ‘little’ forms was accompanied by a decrease of ‘big’ ACTH. The perfusion of fetal adrenal glands with the same immunological quantities of ‘big’, ‘intermediate’ and ‘little’ ACTH showed that the ‘little’ and ‘intermediate’ forms have greater biological potency in eliciting corticosterone secretion than the ‘big’ ACTH form.

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“…Biosynthesis of ACTH and related peptides Although the sequences of ACTH and of α-MSH had been known for almost 15 years, their structural relationship during biosynthesis did not attract much attention until two additional facts were published: (i) the existence of high molecular forms of ACTH and (ii) the discovery of CLIP by Scott et al (1972Scott et al ( , 1974 Roberts and Herbert (1977) and Roberts et al (1978), used a cell-free translation of mRNA from AtT-20 cells. Both studies confirmed the hypothesis that ACTH is biosynthesized as a large precursor form of 28,000-31,000 kDa, which is later transformed into 13-and 4.5-kDa forms.…”

Section: Molecular Forms Of Acth and Lphmentioning

confidence: 99%

“…The sequence of POMC cDNA Although flanking pairs of basic residues had been identified early on as cleavage motifs for the release of β-MSH and β-endorphin from β-LPH (Chrétien & Li 1967) and α-MSH and CLIP from ACTH (Scott et al 1974), the cleavage motif between ACTH and β-LPH could not be established for lack of sufficient amounts of the POMC molecule. The difficulty was circumvented when DNA sequencing came about.…”

Section: Molecular Forms Of Acth and Lphmentioning

confidence: 99%

60 YEARS OF POMC: From the prohormone theory to pro-opiomelanocortin and to proprotein convertases (PCSK1 to PCSK9)

Chrétien

Mbikay

2016

Journal of Molecular Endocrinology

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Pro-opiomelanocortin (POMC), is a polyprotein expressed in the pituitary and the brain where it is proteolytically processed into peptide hormones and neuropeptides with distinct biological activities. It is the prototype of multipotent prohormones. The prohormone theory was first suggested in 1967 when Chrétien and Li discovered γ-lipotropin and observed that (i) it was part of β-lipotropin (β-LPH), a larger polypeptide characterized 2 years earlier and (ii) its C-terminus was β-melanocyte-stimulating hormone (β-MSH). This discovery led them to propose that the lipotropins might be related biosynthetically to the biologically active β-MSH in a precursor to end product relationship. The theory was widely confirmed in subsequent years. As we celebrate the 50th anniversary of the sequencing of β-LPH, we reflect over the lessons learned from the sequencing of those proteins; we explain their extension to the larger POMC precursor; we examine how the theory of precursor endoproteolysis they inspired became relevant for vast fields in biology; and how it led, after a long and arduous search, to the novel proteolytic enzymes called proprotein convertases. This family of nine enzymes plays multifaceted functions in growth, development, metabolism, endocrine, and brain functions. Their genetics has provided many insights into health and disease. Their therapeutic targeting is foreseeable in the near future. Thus, what started five decades ago as a theory based on POMC fragments, has opened up novel and productive avenues of biological and medical research, including, for our own current interest, a highly intriguing hypocholesterolemic Gln152His PCSK9 mutation in French-Canadian families.

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Purification and Characterization of Porcine Corticotrophin-Like Intermediate Lobe Peptide

Cited by 51 publications

References 14 publications

Chemistry and biosynthesis of pro-opiomelanocortin

Chemistry and biosynthesis of pro-opiomelanocortin

Adrenocorticotrophic Hormone in the Anterior and Neurointermediate Lobes of the Rat during the Perinatal Period: Polymorphism, Biological and Immunological Activities of ACTH

60 YEARS OF POMC: From the prohormone theory to pro-opiomelanocortin and to proprotein convertases (PCSK1 to PCSK9)

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