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CGA  -  glycoprotein hormones, alpha polypeptide

Bos taurus

 
 
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Disease relevance of CGA

  • Sf21 insect cells were coinfected with two recombinant baculoviruses, containing the cDNAs of bovine FSH alpha- and beta-subunits respectively [1].
 

High impact information on CGA

  • At an intraluminal pH of 5.5, as found in secretory vesicles, both CGA and CGB bind to the InsP3R [2].
  • In the presence of luminal CGB monomers or CGA/CGB heteromers the InsP3R/Ca2+ channel open probability and mean open time increased significantly [2].
  • Both CGA and CGB associate with inositol 1,4,5-trisphosphate receptor (InsP3R) in a pH-dependent manner [2].
  • Chromogranins A and B (CGA and CGB) are high capacity, low affinity calcium (Ca2+) storage proteins found in many cell types most often associated with secretory granules of secretory cells but also with the endoplasmic reticulum (ER) lumen of these cells [2].
  • To determine whether these IP(3)Rs interact with CGA and CGB, each IP(3)R isoform was co-transfected with CGA or CGB into NIH3T3 or COS-7 cells, and the expressed IP(3)R isoform and CGA or CGB were co-immunoprecipitated [3].
 

Biological context of CGA

  • These modified sites were compared with sequences of others species and discussed in relation with the post-translational modifications that we have reported previously for bovine CGA [4].
  • For chromomycin/Mg2+, the preferred sites on the 70 base pairs of DNA examined are (in decreasing affinity) 3'-GGG, CGA greater than CCG, GCC greater than CGA, CCT greater than CTG-5'. The sequence 3'-CGA-5' has different affinities, indicating the importance of either flanking sequences or a nearly bound drug [5].
  • Interaction between chromogranins and the components of fusion complex also suggests active participation of CGA and CGB in fusion complex formation and subsequent exocytosis [6].
  • This phosphorylation site is close to the processing site (...QKK78HSS(p)81...) yielding vasostatin I, an N-terminal CGA-derived peptide comprising residues 1-76, suggesting that phosphorylation at Ser81 is involved in the formation of vasostatin I in chromaffin cells [7].
 

Anatomical context of CGA

  • 5. The high capacity, low affinity Ca(2+)-binding property of CGB at pH 5.5 is comparable with that of CGA and is in line with its role as a Ca(2+) storage protein in the secretory granules [3].
  • Chromogranins A and B (CGA and CGB), the major proteins of the secretory vesicles of the regulated secretory pathway, have been shown to aggregate in a low pH and high calcium environment, the condition found in the trans-Golgi network where secretory vesicles are formed [8].
  • Suppression of CGA and CGB expression in PC12 cells resulted in 41 and 78% reductions in the number of secretory granules, respectively, while the extents of IP(3)-induced Ca(2+) release in these cells were reduced 40 and 69%, respectively [9].
  • Purification by concanavalin A-Sepharose, Sephacryl S200, and chromatofocusing resulted in a chromaffin granule aspartyl protease (CGAP) that preferred the tachykinin over the enkephalin precursor [10].
 

Associations of CGA with chemical compounds

  • The level of IP(3)-mediated Ca(2+) release in CGA-expressing NIH3T3 cells was 40% higher than in the control cells, while that of CGB-expressing cells was 134% higher, reflecting the number of secretory granules formed [9].
  • The 47- and 16.5-kDa polypeptides of CGAP possessed identical NH2-terminal sequences, suggesting that the 16.5-kDa polypeptide may be derived from the 47-kDa form by proteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)[10]
 

Physical interactions of CGA

  • These data strongly suggest that the 68,000 and 80,000 TSH-receptor complexes are the result of crosslinking to the TSH alpha-beta dimer and not to one subunit in the case of the 68,000 complex and to the TSH alpha-beta dimer in the case of the 80,000 complex, as had been hypothesized previously [11].
 

Other interactions of CGA

 

Analytical, diagnostic and therapeutic context of CGA

  • To further confirm whether the IP(3)R isoforms and CGA and CGB form a complex in the secretory granules the potential interaction between all three isoforms of IP(3)R and CGA and CGB was tested by co-immunoprecipitation experiments of the mixture of secretory granule lysates and the granule membrane proteins [3].
  • CGAP was composed of 47-, 30-, and 16.5-kDa polypeptides migrating as a single band in a nondenaturing electrophoretic gel system, and coeluting with an apparent molecular mass of 45-55 kDa by size-exclusion chromatography [10].

References

  1. High-level expression of biologically active recombinant bovine follicle stimulating hormone in a baculovirus system. van de Wiel, D.F., van Rijn, P.A., Meloen, R.H., Moormann, R.J. J. Mol. Endocrinol. (1998) [Pubmed]
  2. A functional interaction between chromogranin B and the inositol 1,4,5-trisphosphate receptor/Ca2+ channel. Thrower, E.C., Choe, C.U., So, S.H., Jeon, S.H., Ehrlich, B.E., Yoo, S.H. J. Biol. Chem. (2003) [Pubmed]
  3. Localization of three types of the inositol 1,4,5-trisphosphate receptor/Ca(2+) channel in the secretory granules and coupling with the Ca(2+) storage proteins chromogranins A and B. Yoo, S.H., Oh, Y.S., Kang, M.K., Huh, Y.H., So, S.H., Park, H.S., Park, H.Y. J. Biol. Chem. (2001) [Pubmed]
  4. Phosphorylation and O-glycosylation sites of human chromogranin A (CGA79-439) from urine of patients with carcinoid tumors. Gadroy, P., Stridsberg, M., Capon, C., Michalski, J.C., Strub, J.M., Van Dorsselaer, A., Aunis, D., Metz-Boutigue, M.H. J. Biol. Chem. (1998) [Pubmed]
  5. Chromomycin, mithramycin, and olivomycin binding sites on heterogeneous deoxyribonucleic acid. Footprinting with (methidiumpropyl-EDTA)iron(II). Van Dyke, M.W., Dervan, P.B. Biochemistry (1983) [Pubmed]
  6. Presence of syntaxin 1A in secretory granules of chromaffin cells and interaction with chromogranins A and B. Yoo, S.H., You, S.H., Huh, Y.H. FEBS Lett. (2005) [Pubmed]
  7. Mass spectrometric identification of phosphorylated vasostatin II, a chromogranin A-derived protein fragment (1-113). Zhang, X., Dillen, L., Bauer, S.H., Van Dongen, W., Liang, F., Przybylski, M., Esmans, E., De Potter, W.P., Claeys, M. Biochim. Biophys. Acta (1997) [Pubmed]
  8. pH- and Ca(2+)-dependent aggregation property of secretory vesicle matrix proteins and the potential role of chromogranins A and B in secretory vesicle biogenesis. Yoo, S.H. J. Biol. Chem. (1996) [Pubmed]
  9. Effects of chromogranin expression on inositol 1,4,5-trisphosphate-induced intracellular Ca2+ mobilization. Huh, Y.H., Jeon, S.H., Yoo, J.A., Park, S.Y., Yoo, S.H. Biochemistry (2005) [Pubmed]
  10. Purification and characterization of a cathepsin D protease from bovine chromaffin granules. Krieger, T.J., Hook, V.Y. Biochemistry (1992) [Pubmed]
  11. Further studies on the covalent crosslinking of thyrotropin to its receptor: evidence that both the alpha and beta subunits of thyrotropin are crosslinked to the receptor. McQuade, R., Thomas, C.G., Nayfeh, S.N. Arch. Biochem. Biophys. (1987) [Pubmed]
 
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