DOI: 10.1126/science.280.5367.1271. Molecular Basis for Interactions of G Protein βγ Subunits with Effectors

Molecular Basis for Interactions of G Protein βγ Subunits with Effectors

10.1126/science.280.5367.1271

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Both the α and βγ subunits of heterotrimeric guanine nucleotide–binding proteins (G proteins) communicate signals from receptors to effectors. Gβγ subunits can regulate a diverse array of effectors, including ion channels and enzymes. Gα subunits bound to guanine diphosphate (Gα-GDP) inhibit signal transduction through Gβγ subunits, suggesting a common interface on Gβγ subunits for Gα binding and effector interaction. The molecular basis for interaction of Gβγ with effectors was characterized by mutational analysis of Gβ residues that make contact with Gα-GDP. Analysis of the ability of these mutants to regulate the activity of calcium and potassium channels, adenylyl cyclase 2, phospholipase C-β2, and β-adrenergic receptor kinase revealed the Gβ residues required for activation of each effector and provides evidence for partially overlapping domains on Gβ for regulation of these effectors. This organization of interaction regions on Gβ for different effectors and Gα explains why subunit dissociation is crucial for signal transmission through Gβγ subunits.

Bibliography

Ford, C. E., Skiba, N. P., Bae, H., Daaka, Y., Reuveny, E., Shekter, L. R., Rosal, R., Weng, G., Yang, C.-S., Iyengar, R., Miller, R. J., Jan, L. Y., Lefkowitz, R. J., & Hamm, H. E. (1998). Molecular Basis for Interactions of G Protein Î²Î³ Subunits with Effectors. Science, 280(5367), 1271â1274.

Authors 14

Carolyn E. Ford (first)
Nikolai P. Skiba (additional)
Hyunsu Bae (additional)
Yehia Daaka (additional)
Eitan Reuveny (additional)
Lee R. Shekter (additional)
Ramon Rosal (additional)
Gezhi Weng (additional)
Chii-Shen Yang (additional)
Ravi Iyengar (additional)
Richard J. Miller (additional)
Lily Y. Jan (additional)
Robert J. Lefkowitz (additional)
Heidi E. Hamm (additional)

References 28 Referenced 362

10.1146/annurev.pharmtox.37.1.167
10.1074/jbc.272.24.15045
10.1146/annurev.pa.36.040196.002333
10.1016/S0165-6147(96)01001-2
J. A. Pitcher, et al., Science 257, 1264 (1992); Freedman N. J., Lefkowitz R. J., Recent Prog. Horm. Res. 51, 319 (1996). / Recent Prog. Horm. Res. by Freedman N. J. (1996)
10.1016/S0968-0004(97)01061-X
10.1073/pnas.92.19.8601
10.1016/0092-8674(95)90220-1
Cloning of hexahistidine-tagged Gγ1 (H 6 Gγ1) generation of the Gβ1 and H 6 Gγ1 recombinant baculoviruses detailed protocols for recombinant protein expression in Sf9 insect cells and detailed protocols for purification of Gβγ complexes are described at http://www.sciencemag.org/feature/data/976104.shl#9 . The recombinant wild-type Gβγ was equivalent to native Gβγ in the assays used in our study. All mutated Gβ1 subunits assembled properly with H 6 Gγ1 subunits as judged by the trypsin protection assay. We determined with mass spectrometry that the recombinant Gβγ dimers tested were properly modified by isoprenylation and carboxymethylation.
10.1016/S0076-6879(94)37057-5
Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr.
10.1074/jbc.271.1.413
10.1007/s002329900210
10.1073/pnas.94.6.2180
10.1038/360684a0
10.1126/science.1962211
10.1074/jbc.271.41.25071
10.1126/science.7761832
10.1016/0896-6273(95)90101-9
10.1038/380255a0
10.1124/mol.52.2.282
10.1074/jbc.271.30.17597
10.1126/science.278.5345.1907
10.1074/jbc.272.40.25360
10.1074/jbc.272.12.7602
10.1038/379369a0
Recombinant baculovirus containing bovine H 6 Gγ2 cDNA was provided by A. Gilman (University of Texas Southwestern Medical Center Dallas TX). The H 6 -Q227L-Gsα was from T. Patel (University of Tennessee Memphis). The baculovirus vector encoding human PLC-β2 modified with an NH 2 -terminal H 6 tag was provided by A. Smrcka (University of Rochester NY). We thank K. Schey (Medical University of South Carolina Charleston) for performing the mass spectrometry analysis on the recombinant Gβγ proteins.
Supported as follows: Ford Foundation Fellowship (C.E.F.) American Heart Association Grant-In-Aid (N.P.S.) Aaron Diamond Fellowship (G.W.) and both the Mella and Leon Benziyo Center for Neuroscience and Behavioral Research and the Joseph Cohn Center for Biomembrane Research (E.R.). USPHS grants DA02575 DA02121 MH40165 NS33502 DK42086 and DK44840 (R.J.M.); DK38761 and GM54508 (R.I.); and EY06062 and EY10291 (H.E.H.); Howard Hughes Medical Institute (L.Y.J. and R.J.L.) a National Institutes of Mental Health grant to the Silvio Conte Center for Neuroscience at UCSF (L.Y.J.) and both a Distinguished Investigator Award from the National Association for Research in Schizophrenia and Depression and an American Heart Association Grant-in-Aid (H.E.H.).

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:43 a.m.)
Deposited	1 year, 7 months ago (Jan. 12, 2024, 11:38 p.m.)
Indexed	1 day, 21 hours ago (Aug. 30, 2025, 12:26 p.m.)
Issued	27 years, 3 months ago (May 22, 1998)
Published	27 years, 3 months ago (May 22, 1998)
Published Print	27 years, 3 months ago (May 22, 1998)

Funders 0

None

BibTeX

@article{Ford_1998, title={Molecular Basis for Interactions of G Protein βγ Subunits with Effectors}, volume={280}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.280.5367.1271}, DOI={10.1126/science.280.5367.1271}, number={5367}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Ford, Carolyn E. and Skiba, Nikolai P. and Bae, Hyunsu and Daaka, Yehia and Reuveny, Eitan and Shekter, Lee R. and Rosal, Ramon and Weng, Gezhi and Yang, Chii-Shen and Iyengar, Ravi and Miller, Richard J. and Jan, Lily Y. and Lefkowitz, Robert J. and Hamm, Heidi E.}, year={1998}, month=may, pages={1271–1274} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        30
      ]
    ],
    "date-time": "2025-08-30T16:26:01Z",
    "timestamp": 1756571161299
  },
  "reference-count": 28,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "5367",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1998,
        5,
        22
      ]
    ]
  },
  "abstract": "<jats:p>Both the \u03b1 and \u03b2\u03b3 subunits of heterotrimeric guanine nucleotide\u2013binding proteins (G proteins) communicate signals from receptors to effectors. G\u03b2\u03b3 subunits can regulate a diverse array of effectors, including ion channels and enzymes. G\u03b1 subunits bound to guanine diphosphate (G\u03b1-GDP) inhibit signal transduction through G\u03b2\u03b3 subunits, suggesting a common interface on G\u03b2\u03b3 subunits for G\u03b1 binding and effector interaction. The molecular basis for interaction of G\u03b2\u03b3 with effectors was characterized by mutational analysis of G\u03b2 residues that make contact with G\u03b1-GDP. Analysis of the ability of these mutants to regulate the activity of calcium and potassium channels, adenylyl cyclase 2, phospholipase C-\u03b22, and \u03b2-adrenergic receptor kinase revealed the G\u03b2 residues required for activation of each effector and provides evidence for partially overlapping domains on G\u03b2 for regulation of these effectors. This organization of interaction regions on G\u03b2 for different effectors and G\u03b1 explains why subunit dissociation is crucial for signal transmission through G\u03b2\u03b3 subunits.</jats:p>",
  "DOI": "10.1126/science.280.5367.1271",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        27
      ]
    ],
    "date-time": "2002-07-27T09:43:20Z",
    "timestamp": 1027763000000
  },
  "page": "1271-1274",
  "source": "Crossref",
  "is-referenced-by-count": 362,
  "title": "Molecular Basis for Interactions of G Protein \u03b2\u03b3 Subunits with Effectors",
  "prefix": "10.1126",
  "volume": "280",
  "author": [
    {
      "given": "Carolyn E.",
      "family": "Ford",
      "sequence": "first",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Nikolai P.",
      "family": "Skiba",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Hyunsu",
      "family": "Bae",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Yehia",
      "family": "Daaka",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Eitan",
      "family": "Reuveny",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Lee R.",
      "family": "Shekter",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Ramon",
      "family": "Rosal",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Gezhi",
      "family": "Weng",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Chii-Shen",
      "family": "Yang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Ravi",
      "family": "Iyengar",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Richard J.",
      "family": "Miller",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Lily Y.",
      "family": "Jan",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Robert J.",
      "family": "Lefkowitz",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    },
    {
      "given": "Heidi E.",
      "family": "Hamm",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "C. E. Ford, N. P. Skiba, H. Bae, C.-S. Yang, H. E. Hamm, Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA."
        },
        {
          "name": "Y. Daaka and R. J. Lefkowitz, Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA."
        },
        {
          "name": "E. Reuveny, Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot 76100, Israel."
        },
        {
          "name": "L. R. Shekter and R. J. Miller, Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL 60637, USA."
        },
        {
          "name": "R. Rosal, G. Weng, R. Iyengar, Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029, USA."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_3_1_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.pharmtox.37.1.167"
    },
    {
      "key": "e_1_3_1_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.24.15045"
    },
    {
      "key": "e_1_3_1_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.pa.36.040196.002333"
    },
    {
      "key": "e_1_3_1_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0165-6147(96)01001-2"
    },
    {
      "key": "e_1_3_1_6_2",
      "first-page": "319",
      "volume": "51",
      "author": "Freedman N. J.",
      "year": "1996",
      "unstructured": "J. A. Pitcher, et al., Science 257, 1264 (1992); Freedman N. J., Lefkowitz R. J., Recent Prog. Horm. Res. 51, 319 (1996).",
      "journal-title": "Recent Prog. Horm. Res."
    },
    {
      "key": "e_1_3_1_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0968-0004(97)01061-X"
    },
    {
      "key": "e_1_3_1_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.19.8601"
    },
    {
      "key": "e_1_3_1_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90220-1"
    },
    {
      "key": "e_1_3_1_10_2",
      "unstructured": "Cloning of hexahistidine-tagged G\u03b31 (H 6 G\u03b31) generation of the G\u03b21 and H 6 G\u03b31 recombinant baculoviruses detailed protocols for recombinant protein expression in Sf9 insect cells and detailed protocols for purification of G\u03b2\u03b3 complexes are described at http://www.sciencemag.org/feature/data/976104.shl#9 . The recombinant wild-type G\u03b2\u03b3 was equivalent to native G\u03b2\u03b3 in the assays used in our study. All mutated G\u03b21 subunits assembled properly with H 6 G\u03b31 subunits as judged by the trypsin protection assay. We determined with mass spectrometry that the recombinant G\u03b2\u03b3 dimers tested were properly modified by isoprenylation and carboxymethylation."
    },
    {
      "key": "e_1_3_1_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0076-6879(94)37057-5"
    },
    {
      "key": "e_1_3_1_12_2",
      "unstructured": "Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr."
    },
    {
      "key": "e_1_3_1_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.1.413"
    },
    {
      "key": "e_1_3_1_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/s002329900210"
    },
    {
      "key": "e_1_3_1_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.6.2180"
    },
    {
      "key": "e_1_3_1_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/360684a0"
    },
    {
      "key": "e_1_3_1_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1962211"
    },
    {
      "key": "e_1_3_1_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.41.25071"
    },
    {
      "key": "e_1_3_1_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7761832"
    },
    {
      "key": "e_1_3_1_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0896-6273(95)90101-9"
    },
    {
      "key": "e_1_3_1_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/380255a0"
    },
    {
      "key": "e_1_3_1_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1124/mol.52.2.282"
    },
    {
      "key": "e_1_3_1_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.30.17597"
    },
    {
      "key": "e_1_3_1_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.278.5345.1907"
    },
    {
      "key": "e_1_3_1_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.40.25360"
    },
    {
      "key": "e_1_3_1_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.12.7602"
    },
    {
      "key": "e_1_3_1_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/379369a0"
    },
    {
      "key": "e_1_3_1_28_2",
      "unstructured": "Recombinant baculovirus containing bovine H 6 G\u03b32 cDNA was provided by A. Gilman (University of Texas Southwestern Medical Center Dallas TX). The H 6 -Q227L-Gs\u03b1 was from T. Patel (University of Tennessee Memphis). The baculovirus vector encoding human PLC-\u03b22 modified with an NH 2 -terminal H 6 tag was provided by A. Smrcka (University of Rochester NY). We thank K. Schey (Medical University of South Carolina Charleston) for performing the mass spectrometry analysis on the recombinant G\u03b2\u03b3 proteins."
    },
    {
      "key": "e_1_3_1_29_2",
      "unstructured": "Supported as follows: Ford Foundation Fellowship (C.E.F.) American Heart Association Grant-In-Aid (N.P.S.) Aaron Diamond Fellowship (G.W.) and both the Mella and Leon Benziyo Center for Neuroscience and Behavioral Research and the Joseph Cohn Center for Biomembrane Research (E.R.). USPHS grants DA02575 DA02121 MH40165 NS33502 DK42086 and DK44840 (R.J.M.); DK38761 and GM54508 (R.I.); and EY06062 and EY10291 (H.E.H.); Howard Hughes Medical Institute (L.Y.J. and R.J.L.) a National Institutes of Mental Health grant to the Silvio Conte Center for Neuroscience at UCSF (L.Y.J.) and both a Distinguished Investigator Award from the National Association for Research in Schizophrenia and Depression and an American Heart Association Grant-in-Aid (H.E.H.)."
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.280.5367.1271",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        13
      ]
    ],
    "date-time": "2024-01-13T04:38:07Z",
    "timestamp": 1705120687000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.280.5367.1271"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1998,
        5,
        22
      ]
    ]
  },
  "references-count": 28,
  "journal-issue": {
    "issue": "5367",
    "published-print": {
      "date-parts": [
        [
          1998,
          5,
          22
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.280.5367.1271"
  ],
  "URL": "http://dx.doi.org/10.1126/science.280.5367.1271",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        1998,
        5,
        22
      ]
    ]
  }
}