Human Growth Hormone: A Complex of Proteins

Lewis, U. J.; Singh, R. N. P.; Tutwiler, Gene F.; Sigel, Morton B.; VanderLaan, Eileen F.; Vanderlaan, W. P.

doi:10.1016/b978-0-12-571136-4.50019-x

Cited by 118 publications

(82 citation statements)

References 39 publications

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“…Hence, the possible physiological role of such proteolytically modified forms of hGH has been proposed (Lewis et al, 1980). Furthermore, recent studies showed that significant amounts of rat prolactin are secreted by the pituitary gland in the endogenous two-chain form, the relative amount of which increased in conditions associated with enhanced mammary growth such as pregnancy, or perphenazine or oestradiol treatment (Mittra, 1980a).…”

Section: Introductionmentioning

confidence: 99%

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Antigenic, receptor-binding and mitogenic activity of proteolytic fragments of human growth hormone.

Aston¹,

Iványi²

1983

The EMBO Journal

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Analysis of the subtilisin-digested, two-chain form of human growth hormone (hGH) and its constituent polypeptide fragments has been aided by the use of monoclonal antibodies which bind specifically to four distinct epitopes on the native hormone. Using the SDS-polyacrylamide immunoblotting technique, it was shown that one epitope (shared with human chorionic somatomammotropin) detected by EB1 (or EB3) antibody was expressed to a similar extent by both the N-terminal (15 K) and C-terminal (7 K) polypeptides. This epitope is unique in that it represents a repeating determinant within the single chain structure of the hormone. Another three epitopes detected by monoclonal antibodies QA68/NA27, NA71 or NA39/EB2 were absent from the 7-K fragment but were expressed on the 15-K fragment to a similar extent to that on unmodified growth hormone. Binding of NA71 antibody was demonstrated only by radioimmunoassay since this, presumably conformational epitope could not be detected by immunoblotting. The functional importance of the 15-K peptide was demonstrated by its ability to bind specifically to hormone receptors on IM9 human lymphoblastoid cells and by its retention of mitogenicity for the NB2 rat lymphoma ceil line. However, all tested monoclonal antibodies inhibited the binding of [1251]15-K to IM9 cell receptors by either steric hindrance or by an allosteric mechanism and therefore could not be further related topographically to the receptor-binding moiety of hGH.

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Section: Introductionmentioning

confidence: 99%

“…Digestion of hGH with plasmin, thrombin or subtilisin (Li and Bewley, 1976; Lewis et al, 1980;Graf et al, 1981) leads to cleavage in the sequence region 134-149, resulting in a two-chain form which is conformationally similar to the un-*To whom reprint requests should be sent.…”

Section: Introductionmentioning

confidence: 99%

Antigenic, receptor-binding and mitogenic activity of proteolytic fragments of human growth hormone.

Aston¹,

Iványi²

1983

The EMBO Journal

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“…Growth hormone has been demonstrated to exist in a number of forms which include both structural variants derived from alternative processing of mRNA precursors [S] (20 kDa form), as well as variants which are believed to arise from posttranslational modification of the intact molecule by proteases [6]. In the case of the former, it appears that alternative splicing of hGH nuclear RNA precursors results in a deletion of a linear sequence of 15 amino acids near the NH*-terminal Abbreviations: hPRL, human prolactin; hGH, human growth hormone; hCS, human chorionic somatomammotrophin; MAB, monoclonal antibody end of the molecule.…”

Section: Introductionmentioning

confidence: 99%

“…In the case of the former, it appears that alternative splicing of hGH nuclear RNA precursors results in a deletion of a linear sequence of 15 amino acids near the NH*-terminal Abbreviations: hPRL, human prolactin; hGH, human growth hormone; hCS, human chorionic somatomammotrophin; MAB, monoclonal antibody end of the molecule. Proteolytic modification hGH results in cleavage in the sequence region 134-146 [6] and gives rise to a 'two-chain' form composed of two polypeptides of 15 kDa and 7 kDa, respectively.…”

Section: Introductionmentioning

confidence: 99%

Identification of M_r variants of proclatin with monoclonal antibodies

Aston

Young

Berg³

et al. 1984

FEBS Letters

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Monoclonal antibodies (QB01 and 1200) prepared against human proclatin (hPRL) have helped define a variant form of the hormone. This variant is of apparently higher molecular mass (26kDa) than the predominant form of the hormone (24kDa) and its presence does not appear to be species‐restricted. The demonstration of the 26 kDa form of the hPRL in fresh pituitary tissue and amniotic fluid suggests it may retain some specific function.

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“…Compared to the 22 K variant, the 24 K one retains its full immunological and growth-promoting activities (Lewis et al, 1980b) and has enhanced lactogenic activity (Chawla et al, 1983).…”

Section: Introductionmentioning

confidence: 99%