Integration of G protein α (Gα) signaling by the regulator of G protein signaling 14 (RGS14)

Journal of Biological Chemistry

Volumn 290, Issue 14, 2015, Pages 9037-9049

  Brown, Nicole E ^a   Goswami, Devrishi ^b   Branch, Mary Rose ^a   Ramineni, Suneela ^a   Ortlund, Eric A ^a   Griffin, Patrick R ^b   Hepler, John R ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING ENERGY; BINDING SITES; BIOCHEMISTRY; CELL MEMBRANES; CHEMICAL ACTIVATION; ENERGY TRANSFER; HYDROGEN; MASS SPECTROMETRY; MOBILE SECURITY; SIGNALING; SIZE EXCLUSION CHROMATOGRAPHY;

ACTIVATION STATE; BIOLUMINESCENCE RESONANCE ENERGY TRANSFER; CONFORMATIONAL CHANGE; DYNAMIC PROTEINS; HIPPOCAMPAL NEURONS; HYDROGEN/DEUTERIUM EXCHANGE; INTRAMOLECULAR COMMUNICATION; SYNAPTIC PLASTICITY;

PROTEINS;

ALUMINUM DERIVATIVE; ALUMINUM TETRAFLUORIDE; G PROTEIN ALPHA I1; GUANINE NUCLEOTIDE BINDING PROTEIN ALPHA SUBUNIT; GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; GUANOSINE TRIPHOSPHATE; RGS4 PROTEIN; UNCLASSIFIED DRUG; PRIMER DNA; RGS PROTEIN; RGS14 PROTEIN, HUMAN;

ALLOSTERISM; AMINO TERMINAL SEQUENCE; ARTICLE; BINDING AFFINITY; BINDING SITE; BIOLOGICAL MODEL; BIOLUMINESCENCE RESONANCE ENERGY TRANSFER; CARBOXY TERMINAL SEQUENCE; CELL MEMBRANE TRANSPORT; CELLULAR DISTRIBUTION; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DEUTERIUM HYDROGEN EXCHANGE; ENZYME ACTIVITY; G PROTEIN REGULATORY MOTIF; GEL PERMEATION CHROMATOGRAPHY; GENETIC TRANSFECTION; HEK293 CELL LINE; HELA CELL LINE; HIPPOCAMPAL CA2 REGION; HIPPOCAMPAL NEURONAL CULTURE; LONG TERM POTENTIATION; MASS SPECTROMETRY; MOLECULAR DYNAMICS; NERVE CELL PLASTICITY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; SIGNAL TRANSDUCTION; ANIMAL; CYTOLOGY; HUMAN; METABOLISM; NERVE CELL; NUCLEOTIDE SEQUENCE; RAT;

ANIMALS; BASE SEQUENCE; CA2 REGION, HIPPOCAMPAL; DNA PRIMERS; GTP-BINDING PROTEIN ALPHA SUBUNITS; HELA CELLS; HUMANS; NEURONS; RATS; RGS PROTEINS; SIGNAL TRANSDUCTION;

EID: 84926430023     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.634329     Document Type: Article

References (55)

1. Gilman, A. G. (1987) G proteins: transducers of receptor-generated signals. Annu. Rev. Biochem. 56, 615-649
2. Hepler, J. R., and Gilman, A. G. (1992) G proteins. Trends Biochem. 17, 383-387
3. Hamm, H. E. (1998) The many faces of G protein signaling. J. Biol. Chem. 273, 669-672
4. Hollinger, S., and Hepler, J. R. (2002) Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol. Rev. 54, 527-559
5. Ross, E. M., and Wilkie, T. M. (2000) GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGSlike proteins. Annu. Rev. Biochem. 69, 795-827
6. De Vries, L., Zheng, B., Fischer, T., Elenko, E., and Farquhar, M. G. (2000) The regulator of G protein signaling family. Annu. Rev. Pharmacol. Toxicol. 40, 235-271
7. Hollinger, S., Taylor, J. B., Goldman, E. H., and Hepler, J. R. (2001) RGS14 is a bifunctional regulator of Gαi/o activity that exists in multiple populations in brain. J. Neurochem. 79, 941-949
8. Evans, P. R., Lee, S. E., Smith, Y., and Hepler, J. R. (2014) Postnatal developmental expression of regulator of G protein signaling 14 (RGS14) in the mouse brain. J. Comp. Neurol. 522, 186-203
9. Lee, S. E., Simons, S. B., Heldt, S. A., Zhao, M., Schroeder, J. P., Vellano, C. P., Cowan, D. P., Ramineni, S., Yates, C. K., Feng, Y., Smith, Y., Sweatt, J. D., Weinshenker, D., Ressler, K. J., Dudek, S. M., and Hepler, J. R. (2010) RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory. Proc. Natl. Acad. Sci. U.S.A. 107, 16994-16998
10. Vellano, C. P., Lee, S. E., Dudek, S. M., and Hepler, J. R. (2011) RGS14 at the interface of hippocampal signaling and synaptic plasticity. Trends Pharmacol. Sci. 32, 666-674
11. Takesono, A., Cismowski, M. J., Ribas, C., Bernard, M., Chung, P., Hazard, S., 3rd, Duzic, E., and Lanier, S. M. (1999) Receptor-independent activators of heterotrimeric G-protein signaling pathways. J. Biol. Chem. 274, 33202-33205
12. De Vries, L., Fischer, T., Tronchère, H., Brothers, G. M., Strockbine, B., Siderovski, D. P., and Farquhar, M. G. (2000) Activator of G protein signaling 3 is a guanine dissociation inhibitor for Gαi subunits. Proc. Natl. Acad. Sci. U.S.A. 97, 14364-14369
13. Shu, F. J., Ramineni, S., Amyot, W., and Hepler, J. R. (2007) Selective interactions between Giα1 and Giα3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization. Cell. Signal. 19, 163-176
14. Oner, S. S., An, N., Vural, A., Breton, B., Bouvier, M., Blumer, J. B., and Lanier, S. M. (2010) Regulation of the AGS3.Gαi signaling complex by a seven-transmembrane span receptor. J. Biol. Chem. 285, 33949-33958
15. Oner, S. S., Maher, E. M., Breton, B., Bouvier, M., and Blumer, J. B. (2010) Receptor-regulated interaction of activator of G-protein signaling-4 and Gαi. J. Biol. Chem. 285, 20588-20594
16. Willard, F. S., Willard, M. D., Kimple, A. J., Soundararajan, M., Oestreich, E. A., Li, X., Sowa, N. A., Kimple, R. J., Doyle, D. A., Der, C. J., Zylka, M. J., Snider, W. D., and Siderovski, D. P. (2009) Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras effector. PLoS One 4, e4884
17. Shu, F. J., Ramineni, S., and Hepler, J. R. (2010) RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAP kinase signalling pathways. Cell. Signal. 22, 366-376
18. Cho, H., Kozasa, T., Takekoshi, K., De Gunzburg, J., and Kehrl, J. H. (2000) RGS14, a GTPase-activating protein for Giα, attenuates Giα- and G13α-mediated signaling pathways. Mol. Pharmacol. 58, 569-576
19. Traver, S., Bidot, C., Spassky, N., Baltauss, T., De Tand, M. F., Thomas, J. L., Zalc, B., Janoueix-Lerosey, I., and Gunzburg, J. D. (2000) RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of Gαo. Biochem. J. 350, 19-29
20. Kimple, R. J., De Vries, L., Tronchère, H., Behe, C. I., Morris, R. A., Gist Farquhar, M., and Siderovski, D. P. (2001) RGS12 and RGS14 GoLoco motifs are Gαi interaction sites with guanine nucleotide dissociation inhibitor activity. J. Biol. Chem. 276, 29275-29281
21. Mittal, V., and Linder, M. E. (2004) The RGS14 GoLoco domain discriminates among Gαi isoforms. J. Biol. Chem. 279, 46772-46778
22. Blumer, J. B., and Lanier, S. M. (2014) Activators of G protein signaling exhibit broad functionality and define a distinct core signaling triad. Mol. Pharmacol. 85, 388-396
23. Abramow-Newerly, M., Roy, A. A., Nunn, C., and Chidiac, P. (2006) RGS proteins have a signalling complex: interactions between RGS proteins and GPCRs, effectors, and auxiliary proteins. Cell. Signal. 18, 579-591
24. Vellano, C. P., Maher, E. M., Hepler, J. R., and Blumer, J. B. (2011) G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14·Gαi1 complex in live cells. J. Biol. Chem. 286, 38659-38669
25. Vellano, C. P., Shu, F. J., Ramineni, S., Yates, C. K., Tall, G. G., and Hepler, J. R. (2011) Activation of the regulator of G protein signaling 14-Gαi1-GDP signaling complex is regulated by resistance to inhibitors of cholinesterase-8A. Biochemistry 50, 752-762
26. Vellano, C. P., Brown, N. E., Blumer, J. B., and Hepler, J. R. (2013) Assembly and function of the regulator of G protein signaling 14 (RGS14)·H-Ras signaling complex in live cells are regulated by Gαi1 and Gαi-linked GPCRs. J. Biol. Chem. 288, 3620-3631
27. Goswami, D., Devarakonda, S., Chalmers, M. J., Pascal, B. D., Spiegelman, B. M., and Griffin, P. R. (2013) Time window expansion for HDX analysis of an intrinsically disordered protein. J. Am. Soc. Mass Spectrom. 24, 1584-1592
28. Pascal, B. D., Willis, S., Lauer, J. L., Landgraf, R. R., West, G. M., Marciano, D., Novick, S., Goswami, D., Chalmers, M. J., and Griffin, P. R. (2012) HDX workbench: software for the analysis of H/D exchange MS data. J. Am. Soc. Mass Spectrom. 23, 1512-1521
29. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., and Ferrin, T. E. (2004) UCSF Chimera: a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612
30. Sievers, F., Wilm, A., Dineen, D., Gibson, T. J., Karplus, K., Li, W., Lopez, R., McWilliam, H., Remmert, M., Söding, J., Thompson, J. D., and Higgins, D. G. (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539
31. Goujon, M., McWilliam, H., Li, W., Valentin, F., Squizzato, S., Paern, J., and Lopez, R. (2010) A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Res. 38, W695-W699
32. Berman, D. M., Kozasa, T., and Gilman, A. G. (1996) The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis. J. Biol. Chem. 271, 27209-27212
33. Chen, C. K., Wieland, T., and Simon, M. I. (1996) RGS-r, a retinal specific RGS protein, binds an intermediate conformation of transducin and enhances recycling. Proc. Natl. Acad. Sci. U.S.A. 93, 12885-12889
34. Watson, N., Linder, M. E., Druey, K. M., Kehrl, J. H., and Blumer, K. J. (1996) RGS family members: GTPase-activating proteins for heterotrimeric G-protein α-subunits. Nature 383, 172-175
35. Goswami, D., Callaway, C., Pascal, B. D., Kumar, R., Edwards, D. P., and Griffin, P. R. (2014) Influence of domain interactions on conformational mobility of the progesterone receptor detected by hydrogen/deuterium exchange mass spectrometry. Structure 22, 961-973
36. Landgraf, R. R., Goswami, D., Rajamohan, F., Harris, M. S., Calabrese, M. F., Hoth, L. R., Magyar, R., Pascal, B. D., Chalmers, M. J., Busby, S. A., Kurumbail, R. G., and Griffin, P. R. (2013) Activation of AMP-activated protein kinase revealed by hydrogen/deuterium exchange mass spectrometry. Structure 21, 1942-1953
37. Marciano, D. P., Dharmarajan, V., and Griffin, P. R. (2014) HDX-MS guided drug discovery: small molecules and biopharmaceuticals. Curr. Opin. Struct. Biol. 28, 105-111
38. Mixon, M. B., Lee, E., Coleman, D. E., Berghuis, A. M., Gilman, A. G., and Sprang, S. R. (1995) Tertiary and quaternary structural changes in Giα1 induced by GTP hydrolysis. Science 270, 954-960
39. Chung, K. Y., Rasmussen, S. G., Liu, T., Li, S., DeVree, B. T., Chae, P. S., Calinski, D., Kobilka, B. K., Woods, V. L., Jr., and Sunahara, R. K. (2011) Conformational changes in the G protein Gs induced by the β2 adrenergic receptor. Nature 477, 611-615
40. Soundararajan, M., Willard, F. S., Kimple, A. J., Turnbull, A. P., Ball, L. J., Schoch, G. A., Gileadi, C., Fedorov, O. Y., Dowler, E. F., Higman, V. A., Hutsell, S. Q., Sundström, M., Doyle, D. A., and Siderovski, D. P. (2008) Structural diversity in the RGS domain and its interaction with heterotrimeric G protein α-subunits. Proc. Natl. Acad. Sci. U.S.A. 105, 6457-6462
41. Tesmer, J. J. (2009) Structure and function of regulator of G protein signaling homology domains. Prog. Mol. Biol. Transl. Sci. 86, 75-113
42. Bosch, D. E., Willard, F. S., Ramanujam, R., Kimple, A. J., Willard, M. D., Naqvi, N. I., and Siderovski, D. P. (2012) A P-loop mutation in Galpha subunits prevents transition to the active state: implications for G-protein signaling in fungal pathogenesis. PLoS Pathog. 8, e1002553
43. Du, Q., and Macara, I. G. (2004) Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119, 503-516
44. Bosch, D. E., Kimple, A. J., Sammond, D. W., Muller, R. E., Miley, M. J., Machius, M., Kuhlman, B., Willard, F. S., and Siderovski, D. P. (2011) Structural determinants of affinity enhancement between GoLoco motifs and G-protein α subunit mutants. J. Biol. Chem. 286, 3351-3358
45. Kiel, C., Wohlgemuth, S., Rousseau, F., Schymkowitz, J., Ferkinghoff-Borg, J., Wittinghofer, F., and Serrano, L. (2005) Recognizing and defining true Ras binding domains II: in silico prediction based on homology modelling and energy calculations. J. Mol. Biol. 348, 759-775
46. Mittal, V., and Linder, M. E. (2006) Biochemical characterization of RGS14: RGS14 activity towards G-protein α subunits is independent of its binding to Rap2A. Biochem. J. 394, 309-315
47. Tu, Y., Popov, S., Slaughter, C., and Ross, E. M. (1999) Palmitoylation of a conserved cysteine in the regulator of G protein signaling (RGS) domain modulates the GTPase-activating activity of RGS4 and RGS10. J. Biol. Chem. 274, 38260-38267
48. Ishii, M., Fujita, S., Yamada, M., Hosaka, Y., and Kurachi, Y. (2005) Phosphatidylinositol 3,4,5-trisphosphate and Ca2+/calmodulin competitively bind to the regulators of G-protein-signalling (RGS) domain of RGS4 and reciprocally regulate its action. Biochem. J. 385, 65-73
49. Popov, S. G., Krishna, U. M., Falck, J. R., and Wilkie, T. M. (2000) Ca2+/calmodulin reverses phosphatidylinositol 3,4,5-trisphosphate-dependent inhibition of regulators of G protein-signaling GTPase-activating protein activity. J. Biol. Chem. 275, 18962-18968
50. Evans, P. R., and Hepler, J. R. (2012) Regulator of G protein signaling 14 (RGS14) interacts with calmodulin (CaM) in a calcium-dependent manner. 42nd Annual Meetiing of the Society for Neuroscience, New Orleans, October 13-17, 2012, Society for Neuroscience
51. Panja, D., and Bramham, C. R. (2014) BDNF mechanisms in late LTP formation: a synthesis and breakdown. Neuropharmacology 76, 664-676
52. Kennedy, M. B., Beale, H. C., Carlisle, H. J., and Washburn, L. R. (2005) Integration of biochemical signalling in spines. Nat. Rev. Neurosci. 6, 423-434
53. Hollinger, S., Ramineni, S., and Hepler, J. R. (2003) Phosphorylation of RGS14 by protein kinase A potentiates its activity toward Gαi. Biochemistry 42, 811-819
54. Hollinger, S., and Hepler, J. R. (2004) Methods for measuring RGS protein phosphorylation by G protein-regulated kinases. Methods Mol. Biol. 237, 205-219
55. Traver, S., Splingard, A., Gaudriault, G., and Gunzburg, J. D. (2004) The RGS (regulator of G protein signalling) and GoLoco domains of RGS14 co-operate to regulate Gi-mediated signalling. Biochem. J. 379, 627-632