Growth hormone receptor and serum binding protein: purification, cloning and expression

Leung, David W. M.; Spencer, Steven A.; Cachianes, George; Hammonds, R. Glenn; Collins, C Olin; Henzel, William J.; Barnard, Ross; Waters, Michael J.; Wood, William I.

doi:10.1038/330537a0

Cited by 1,539 publications

(689 citation statements)

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“…Our model arose from a consideration of how one gp130 molecule might interact with two distinct sites on different E-6 molecules, as well as the nature of the site III interaction. We have taken into account that the extracellular region of gp130 has the same modular structure as the G-CSFR , Hibi et al, 1990Larsen et al, 1990), including an Ig-like domain that is lacking in the GHR (Leung et al, 1987). Both the Ig-like domain and the CBD of the G-CSFR are required for ternary complex formation with G-CSF (Hiraoka et al, 1995).…”

Section: The High Affinity Ternary Il-6 Receptor-complex Is a Hexamermentioning

confidence: 99%

Interleukin‐6: Structure‐function relationships

et al. 1997

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Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-1 1, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affhity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.

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Section: The High Affinity Ternary Il-6 Receptor-complex Is a Hexamermentioning

confidence: 99%

Interleukin‐6: Structure‐function relationships

et al. 1997

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“…GHBP, which has the same structure as the extracellular domain of the GH receptor, is assumed to reflect the tissue GHreceptor concentration as a part of the GH axis [18,19].…”

Section: Discussionmentioning

confidence: 99%

Nutrition Related Hormonal Changes in Obese Children.

et al. 1998

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Abstract. Children with simple obesity (SO) show increased linear growth with normal or high serum insulin-like growth factor-I (IGF-I) levels during prepubertal period, despite low GH secretion. We measured IGF-I, IGFBP-1, GHBP and other factors to clarify the hormonal relation between the nutrition and the linear growth in SO and compared these factors with children with normal short stature (NS). Subjects were 23 SO and 19 NS children, and their height standard deviation (SD) scores were 0.7 ± 0.2 SD and -3.4 ± 0.3 SD (mean ± SEM) (P<0.01), respectively. Oral glucose tolerance test (OGTT) was performed in all the subjects and GH-releasing factor (GRF) test was also performed in 13 of SO and 17 of NS. The peak levels of GH in the GRF test were significantly lower in SO than in NS (12.8 ± 1.7 vs. 39.8 ± 6.9 ng/ml) and showed a significantly positive correlation with IGFBP-1 (r= 0.63, P<0.01). Serum GHBP level and IGF-I level were significantly higher in SO than in NS on pubertal stage matching. There was a positive correlation between GHBP and insulin during OGTT (r=0.75, P<0.01). When the sum of the values during OGTT was expressed as L insulin, ~C-peptide and glucose were significantly higher in SO than in NS on pubertal stage matching. Basal and IGFBP-1 were significantly lower in SO than in NS, but IGFBP-3 levels showed no significant difference between the two groups either in prepuberty or midpuberty.In conclusion, it can be hypothesized that the overnutrition causes hyperinsulinemia which increases GH receptor and IGF-I secretion despite low GH secretion. Hyperinsulinemia also may increase free IGF-I by lowering IGFBP-1. These two mechanism are supposed to be the nutrition related hormonal changes in SO and can explain the growth of SO. In addition, the increased free IGF-I may contribute the decreased GH secretion due to negative feedback in SO.

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“…variety of in vivo substrates of the ubiquitin conjugating system have been identified, including histones [10], actin [11], cytlins [12], the tumor suppressor p53 [13,14], MATch2 transcr ption repressor [15], cell surface receptors [16][17][18], c-jun [19] and NF~cB [20]. Some ubiquitin conjugating enzymes are able to transfer ubiquitin to the model substrate histone in vitro without any accessory factors, such as E3s.…”

Section: Introductionmentioning

confidence: 99%

Characterization of functionally independent domains in the human ubiquitin conjugating enzyme UbcH2

et al. 1995

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UbcH2 encodes a human ubiquitin conjugating enzyme (E2) able to conjugate ubiquitin to histone H2A in an E3 independent manner in vitro, which indicates that UbcH2 directly interacts with its substrates. To identify parts of the enzyme that are capable of binding H2A, we expressed several deletion mutants of UbcH2 in E. coli and tested the ability of the affinity purified mutant proteins to ubiquitinate H2A in the presence of bacterial expressed E1 and ubiquitin. With this in vitro assay we identified a C-terminal part of UbcH2 to be important for the interaction with H2A. Transfer of this C-terminal domain to another human E2, which is unable to catalyze ubiquitination of histories, leads to a fully active hybrid human ubiquitin conjugating enzyme capable of H2A ubiquitination. These results demonstrate that UbcH2 consists of two functionally independent domains. A N-terminal core domain with ubiquitin conjugating activity, and a C-terminal domain which interacts with substrate proteins.

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Growth hormone receptor and serum binding protein: purification, cloning and expression

Cited by 1,539 publications

References 0 publications

Interleukin‐6: Structure‐function relationships

Interleukin‐6: Structure‐function relationships

Nutrition Related Hormonal Changes in Obese Children.

Characterization of functionally independent domains in the human ubiquitin conjugating enzyme UbcH2

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