| RRC ID |
39105
|
| 著者 |
Wada M, Uchida H, Ikeda M, Tsunekawa B, Naito N, Banba S, Tanaka E, Hashimoto Y, Honjo M.
|
| タイトル |
The 20-kilodalton (kDa) human growth hormone (hGH) differs from the 22-kDa hGH in the complex formation with cell surface hGH receptor and hGH-binding protein circulating in human plasma.
|
| ジャーナル |
Mol Endocrinol
|
| Abstract |
In spite of recent advance in understanding of the stoichiometry of 22-kDa human GH (22K-hGH) with cell surface hGH receptor (hGHR) and hGH-binding protein (hGH-BP) circulating in human plasma, that of 20-kDa hGH (20K-hGH) is poorly understood. To clarify this, mouse pro-B Ba/F3 cells stably expressing the full-length hGHR (Ba/F3-hGHR) and both recombinant and native hGH-BP were used in this study. Cell proliferation assay revealed that the two hGH isoforms increased Ba/F3-hGHR cells to the same extent in a dose-dependent manner at 0.1 pM-10 nM. However, the self-inhibition observed in 20K-hGH at 5 microM was significantly less than that in 22K-hGH. Furthermore, addition of 1 and 10 nM recombinant hGH-BP caused a slight inhibition in 20K-hGH, but a drastic inhibition in 22K-hGH. Gel filtration chromatography of mixtures of 20K-hGH with recombinant hGH-BP clearly demonstrated that 20K-hGH formed a 1:2 (hGH:hGH-BP) complex efficiently but no detectable 1:1 complex in any conditions. Supporting data were also obtained with native hGH-BP. Computer-aided homology modeling of 20K-hGH has provided speculative data that the conformational change caused by deletion of 15 residues may occur only in the loop between helix 1 and helix 2, resulting in the reduction of its site 1 affinity. In conclusion, 20K-hGH possesses a unique property for forming a 1:2 complex to the same extent as 22K-hGH but has difficulty in forming a 1:1 complex, which might be attributed to the conformational change restricted to its site 1 region.
|
| 巻・号 |
12(1)
|
| ページ |
146-56
|
| 公開日 |
1998-1-1
|
| DOI |
10.1210/mend.12.1.0054
|
| PMID |
9440818
|
| MeSH |
Animals
Carrier Proteins / blood*
Carrier Proteins / physiology
Cell Division / drug effects
Cell Line
Chromatography, Gel
Dose-Response Relationship, Drug
Human Growth Hormone / blood*
Human Growth Hormone / physiology*
Humans
Macromolecular Substances
Mice
Models, Molecular
Receptors, Somatotropin / blood*
Receptors, Somatotropin / physiology*
Sequence Homology, Amino Acid
|
| IF |
3.628
|
| 引用数 |
66
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
Ba/F3(RCB0805) |
