DOI: 10.1073/pnas.96.4.1327. Posttranslational modification of Gα <sub>o1</sub> generates Gα <sub>o3</sub> , an abundant G protein in brain

Posttranslational modification of Gα o1 generates Gα o3 , an abundant G protein in brain

10.1073/pnas.96.4.1327

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Gα o , the most abundant G protein in mammalian brain, occurs at least in two subforms, i.e., Gα o1 and Gα o2 , derived by alternative splicing of the mRNA. A third Gα o1 -related isoform, Gα o3 , has been purified, representing about 30% of total G o in brain. Initial studies revealed distinct biochemical properties of Gα o3 as compared with other Gα o isoforms. In matrix-assisted laser desorption/ionization peptide mass mapping of gel-isolated Gα o1 and Gα o3 , C-terminal peptides showed a difference of +1 Da for Gα o3 . Nanoelectrospray tandem mass spectrometry sequencing revealed an Asp instead of an Asn at position 346 of Gα o3 . Gel electrophoretic analysis of recombinant Gα o3 showed the same mobility as native Gα o3 but distinct to Gα o1 . The conversion of 346 Asn→Asp changed the signaling properties, including the velocity of the basal guanine nucleotide-exchange reaction, which points to the involvement of the C terminus in basal guanosine 5′-[γ-thio]triphosphate binding. No cDNA coding for Gα o3 was detected, suggesting an enzymatic deamidation of Gα o1 by a yet-unidentified activity. Therefore, Gα heterogeneity is generated not only at the DNA or RNA levels, but also at the protein level. The relative amount of Gα o1 and Gα o3 differed from cell type to cell type, indicating an additional principle of G protein regulation.

Bibliography

Exner, T., Jensen, O. N., Mann, M., Kleuss, C., & NÃ¼rnberg, B. (1999). Posttranslational modification of GÎ± o1 generates GÎ± o3 , an abundant G protein in brain. Proceedings of the National Academy of Sciences, 96(4), 1327â1332.

Authors 5

Torsten Exner (first)
Ole N. Jensen (additional)
Matthias Mann (additional)
Christiane Kleuss (additional)
Bernd Nürnberg (additional)

References 56 Referenced 37

10.1007/BF01200143
10.1146/annurev.pharmtox.37.1.167
10.1074/jbc.273.2.669
10.1126/science.1902986
10.1016/0165-6147(84)90444-9
J Moss, M Vaughan Adv Enzymol Relat Areas Mol Biol 61, 303–379 (1988). / Adv Enzymol Relat Areas Mol Biol by Moss J (1988)
10.1073/pnas.89.13.5720
10.1074/jbc.270.2.503
10.1146/annurev.bi.65.070196.001325
10.1016/S0021-9258(18)89881-7
10.1016/S0021-9258(18)89817-9
10.1038/344836a0
10.1073/pnas.87.17.6477
10.1016/S0021-9258(17)44790-9
10.1016/S0021-9258(19)38579-5
10.1016/0014-5793(92)80770-H
10.1016/0962-8924(93)90122-H
10.1073/pnas.94.5.1727
10.1073/pnas.95.6.3269
10.1016/0896-6273(95)90254-6
10.1038/380258a0
10.1038/380255a0
10.1038/385446a0
10.1073/pnas.94.16.8866
10.1016/0014-5793(96)00584-4
10.1093/emboj/17.2.406
10.1016/0014-5793(89)81815-0
10.1111/j.1471-4159.1990.tb04903.x
10.1111/j.1471-4159.1990.tb05773.x
10.2337/diab.41.11.1390
10.1074/jbc.270.9.4189
10.1042/bj3000387
10.1111/j.1469-7793.1997.321bk.x
10.1016/0014-5793(90)81416-L
10.1016/0014-5793(91)80814-J
10.1038/379466a0
10.1074/jbc.273.12.7024
O N Jensen, A Shevchenko, M Mann Protein Analysis by Mass Spectrometry, ed T E Creighton (IRL, Oxford), pp. 29–57 (1997a). / Protein Analysis by Mass Spectrometry by Jensen O N (1997)
10.1073/pnas.88.8.2974
10.1074/jbc.270.4.1734
E Padrell, D J Carty, T M Moriarty, J D Hildebrandt, E M Landau, R Iyengar J Biol Chem 259, 13806–13813 (1991). / J Biol Chem by Padrell E (1991)
10.1111/j.1432-1033.1992.tb17461.x
10.1021/bi00418a062
10.1111/j.1432-1033.1989.tb21099.x
10.1016/0076-6879(91)95164-F
J J Murtagh, R Eddy, T B Shows, J Moss, M Vaughan Mol Cell Biol 11, 1146–1155 (1991). / Mol Cell Biol by Murtagh J J (1991)
10.1073/pnas.87.10.3645
10.1038/27831
10.1146/annurev.biochem.66.1.639
10.1073/pnas.95.8.4270
10.1074/jbc.273.6.3247
10.1016/S0021-9258(17)36711-X
10.1126/science.3381086
10.1038/42743
10.1038/42735
Anis Y. Nürnberg B. Reiss N. Naor Z. Visochek L. & Cohen-Armon M. (1999) J. Biol. Chem. in press.

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:39 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:58 p.m.)
Indexed	1 month, 4 weeks ago (July 2, 2025, 1:29 p.m.)
Issued	26 years, 6 months ago (Feb. 16, 1999)
Published	26 years, 6 months ago (Feb. 16, 1999)
Published Online	26 years, 6 months ago (Feb. 16, 1999)
Published Print	26 years, 6 months ago (Feb. 16, 1999)

Funders 0

None

BibTeX

@article{Exner_1999, title={Posttranslational modification of Gα o1 generates Gα o3 , an abundant G protein in brain}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.4.1327}, DOI={10.1073/pnas.96.4.1327}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Exner, Torsten and Jensen, Ole N. and Mann, Matthias and Kleuss, Christiane and Nürnberg, Bernd}, year={1999}, month=feb, pages={1327–1332} }

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