Mutagenesis and chimeric genes define determinants in the beta subunits of human chorionic gonadotropin and lutropin for secretion and assembly.

The Journal of Cell Biology
M M MatzukI Boime

Abstract

Chorionic gonadotropin (CG) and lutropin (LH) are members of a family of glycoprotein hormones that share a common alpha subunit but differ in their hormone-specific beta subunits. The glycoprotein hormone beta subunits share a high degree of amino acid homology that is most evident for the LH beta and CG beta subunits having greater than 80% sequence similarity. However, transfection studies have shown that human CG beta and alpha can be secreted as monomers and can combine efficiently to form dimer, whereas secretion and assembly of human LH beta is less efficient. To determine which specific regions of the LH beta and CG beta subunits are responsible for these differences, mutant and chimeric LH beta-CG beta genes were constructed and transfected into CHO cells. Expression of these subunits showed that both the hydrophobic carboxy-terminal seven amino acids and amino acids Trp8, Ile15, Met42, and Asp77 together inhibit the secretion of LH beta. The carboxy-terminal amino acids, along with Trp8, Ile15, Met42, and Thr58 are implicated in the delayed assembly of LH beta. These unique features of LH beta may also play an important role in pituitary intracellular events and may be responsible for the differential glycosylation an...Continue Reading

References

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Citations

May 1, 1992·Molecular and Cellular Endocrinology·D D VakhariaJ A Dias
Feb 1, 1992·Molecular and Cellular Endocrinology·R K CampbellW R Moyle
Sep 21, 2002·Molecular and Cellular Endocrinology·Vicenta Garcia-CampayoIrving Boime
Mar 15, 2000·Molecular and Cellular Endocrinology·S SuzukiN Suganuma
Feb 13, 2001·Trends in Endocrinology and Metabolism : TEM·V Garcia-Campayo, I Boime
Jul 1, 1997·Nature Biotechnology·V Garcia-CampayoI Boime
Dec 17, 2004·The New England Journal of Medicine·Hernán Valdes-SocinAlbert Beckers
Sep 1, 2007·The New England Journal of Medicine·Adriana Lofrano-PortoFrancisco de Assis da Rocha Neves
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·F A FaresI Boime
Mar 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·T SugaharaI Boime
May 16, 2009·Endocrinology·Pratibhasri A VardhanaJoyce W Lustbader
Jan 10, 2009·Molecular Endocrinology·Albina Jablonka-Shariff, Irving Boime
Mar 31, 1999·Endocrinology·J H StahlS A Camper
Feb 23, 2008·The Journal of Biological Chemistry·Albina Jablonka-ShariffIrving Boime
Aug 15, 2001·European Journal of Biochemistry·D DirnbergerD van de Wiel

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