Publications

Montanez-Miranda C, Perszyk RE, Harbin NH, Okalova J, Ramineni, S, Traynelis SF, and Hepler JR (2022)  Functional assessment of cancer-linked mutations in sensitive regions of RGS proteins predicted by 3DMTR analysis. Mol Pharmacol., accepted in press. 

Friedman PA, Sneddon WB, Mamonova T, Montanez-Miranda C, Ramineni S, Harbin NH, Squires KE, Gefter JV, Magyar CE, Emlet DR, Hepler JR (2022) RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein. J Biol Chem. May;298(5):101836. doi: 10.1016/j.jbc.2022.101836. Epub 2022 Mar 17. PMID: 35307350 Abstract

Foster SL, Lustberg DJ, Harbin NH, Bramlett SN, Hepler JR*, Weinshenker D.* (2021) RGS14 modulates locomotor behavior and ERK signaling induced by environmental novelty and cocaine within discrete limbic structures. Psychopharmacology (Berl). Oct;238(10):2755-2773. doi: 10.1007/s00213-021-05892-x. Epub 2021 Jun 29. PMID: 34184126 *Co-corresponding authors Abstract

Harbin NH, Bramlett SN, Montanez-Miranda C, Terzioglu G, Hepler JR (2021) RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain. Int J Mol Sci. Jun 25;22(13):6823. doi: 10.3390/ijms22136823. PMID: 34201943 Abstract

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Introduction and Other Protein Targets. Alexander SP, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Southan C, Buneman OP, Cidlowski JA, Christopoulos A, Davenport AP, Fabbro D, Spedding M, Striessnig J, Davies JA, Ahlers-Dannen KE, Alqinyah M, Arumugam TV, Bodle C, Dagner JB, Chakravarti B, Choudhuri SP, Druey KM, Fisher RA, Gerber KJ, Hepler JR, Hooks SB, Kantheti HS, Karaj B, Layeghi-Ghalehsoukhteh S, Lee JK, Luo Z, Martemyanov K, Mascarenhas LD, McNabb H, Montañez-Miranda C, Ogujiofor O, Phan H, Roman DL, Shaw V, Sjogren B, Sobey C, Spicer MM, Squires KE, Sutton L, Wendimu M, Wilkie T, Xie K, Zhang Q, Zolghadri Y. Br J Pharmacol. 2021 Oct;178 Suppl 1:S1-S26. doi: 10.1111/bph.15537. PMID: 34529830

Squires KE, Gerber KJ, Tillman MC, Lustberg DJ, Montañez-Miranda C, Zhao M, Ramineni S, Scharer CD, Saha RN, Shu FJ, Schroeder JP, Ortlund EA, Weinshenker D, Dudek SM, Hepler JR. (2020) Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons. J Biol Chem. 296:100024. doi: 10.1074/jbc.RA120.016009. Epub 2020 Nov 22. PMID: 33410399 Abstract

Gerber KJ, Dammer EB, Duong DM, Deng Q, Dudek SM, Seyfried NT, Hepler JR (2019) Specific Proteomes of Hippocampal Regions CA2 and CA1 Reveal Proteins Linked to the Unique Physiology of Area CA2. J Proteome Res. Jun 7;18(6):2571-2584. doi: 10.1021/acs.jproteome.9b00103. Epub 2019 May 14. PMID: 31059263 Abstract

Brown, N.E., Blumer, J.B., and Hepler, J.R. (2015) Bioluminescence Resonance Energy Transfer to Detect Protein-Protein Interactions in Live Cells. In: Protein-Protein Interactions: Methods and Applications, Methods in Molecular Biology , 1278:457-65. Abstract

Brown, N.E., Goswami, D., Branch, M.R., Ramineni, S., Ortlund, E.A., Griffin, P.R. and Hepler, J.R. (2015) Integration of G protein alpha (Gα) Signaling by the Regulator of G protein Signaling 14 (RGS14). J. Biol. Chem ., Apr 3;290(14):9037-49. Abstract

Evans, P.R., Dudek, S. M., and Hepler, J.R. (2015) Regulator of G Protein Signaling 14: A Molecular Break on Synaptic Plasticity Linked to Learning and Memory. Prog Mol Biol Transl Sci., in press.

Brown, N.E., Lambert, N.A and Hepler, J.R. (2016) RGS14 regulates the lifetime of Gα-GTP signaling but does not prolong Gβγ signaling following receptor activation in live cells. Pharmacol Res Perspectives. Aug 18;4(5):e00249. Abstract

Gerber, K.J., Squires, K.E. and Hepler, J.R. (2016) Roles for Regulator of G protein Signaling (RGS)Proteins in Synaptic Signaling and Plasticity. Molecular Pharmacology, 89:273-86. Abstract

Squires*, K.E., Gerber*, K.J., Pare, J., Branch, M.R., Smith, Y., and Hepler, J.R. (2017) Regulator of G Protein Signaling 14 (RGS14) is Expressed Pre- and Postsynaptically in Neurons of Hippocampus, Basal Ganglia, and Amygdala of Monkey and Human Brain. Brain Structure and Function, doi: 10.1007/s00429-017-1487-y. [Epub ahead of print] PMID: 28776200 * Co-first authors. Abstract

Branch, M.R. and Hepler, J.R. (2017) Endogenous RGS14 is a cytosolic-nuclear shuttling protein that localizes to juxtanuclear membranes and chromatin-rich regions of the nucleus. PLOS ONE , 12(9):e0184497. doi: 10.1371/journal.pone.0184497. Abstract

Zou, J., Salarian, M., Chen, Y., Zhuo, Y., Brown, N.E., Hepler, J.R and Yang, J. (2017) Direct Visualization of Interaction between Calmodulin and Connexin 45. Biochemical J., 474(24):4035-4051. doi: 10.1042/BCJ20170426. Abstract

Evans, P.R., Gerber, K.J., Ramineini, S., Yang. J., Griffin, P., Seyfried, N.J., and Hepler, J.R. (2018) Interactome Analysis Reveals Regulator of G Protein Signaling 14 (RGS14) is a Novel Calcium/Calmodulin (Ca⁺⁺/CaM) and CaM Kinase II (CaMKII) binding partner. J Proteome Res., Apr 6;17(4):1700-1711. doi: 10.1021/acs.jproteome.8b00027. Epub 2018 Mar 20. Online at BIORXIV as preprint: MS ID#: BIORXIV/2018/247270. Abstract

Evans, P.R., Parra-Bueno, P., Smirnov, M.S., Lustberg, D.J., S., Dudek, S.M., Hepler, J.R.* and Yasuda, R.* (2018) RGS14 restricts plasticity in hippocampal CA2 by limiting postsynaptic calcium signaling. eNeuro, Jun 4;5(3). pii: ENEURO.0353-17.2018.. April 30, doi: 10.1523/ENEURO.0353-17.2018 Online at BIORXIV MS ID#: doi * Co-corresponding authors. Abstract

Squires, K.H., Montanez-Miranda, C., Pandya, R. R., Torres, M.P. and Hepler, J.R. (2018) Genetic analysis of rare human variants in Regulators of G Protein Signaling (RGS) Proteins and their roles in physiology and disease. Pharmacological Reviews, Jul;70(3):446-474. Mar 30: Pharmacological Reviews article. Abstract

Gerber, K.J., Squires, K.H. and Hepler, J.R. (2018) 14-3-3g binds RGS14 at distinct sites to inhibit the RGS14:Gai-AlF₄^- signaling complex and RGS14 nuclear localization. J. Biol. Chem., Accepted (in press).

Ghil, SH, McCoy, K.L. and Hepler, J.R. (2014) RGS2 and RGS4 form distinct G protein-dependent complexes with protease activated recepetor-1 (PAR1) in live cells. PLoS ONE, 9(4):e95355. Doi:10.1371. Abstract

Hepler, J.R. (2014) G protein coupled receptor signaling complexes in live cells. Cellular Logistic, 4(1):e29392. Abstract

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 (1): 186-203. (DOI:10.1002/cne.23395 (online pub, Nov 26, 2013). Abstract

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 complex is regulated by Gαi1 and a Gi-linked GPCR. J. Biol. Chem., 288(5):3620-31. doi: 10.1074/jbc.M112.440057. Epub 2012 Dec 17. PMID: 23250758 Abstract

Zhao, P., Nunn, C., Ramineni, S., Hepler, J.R. and Chidiac, P. (2012) The Ras-binding domain of RGS14 regulates its functional interactions with heterotrimeric G proteins. J. Cell. Biochem., 114(6): 1414-1423. doi: 10.1002/jcb.24483. Abstract

McCoy, K.L., Gyoneva, S., Vellano, C.P., Smrcka A.V., Traynelis, S.F. and Hepler, J.R. (2012) Protease-Activated Receptor 1 (PAR1) coupling to Gq/11 but not to Gi/o or G12/13 is mediated by discrete amino acids within the receptor second intracellular loop. Cellular Signalling, 24(6):1351-60. Abstract

Vellano, C.P., Maher, E.M., Hepler, J.R. and Blumer, J.B. (2011) G protein coupled receptors and Ric-8A both regulate the Regulator of G protein Signaling 14 (RGS14):Gαi1 complex in living cells. J. Biol. Chem. 286(44): 38659-3866. Abstract

Vellano, C.P, Lee, S.E., Dudek, S.M. and Hepler, J.R. (2011) RGS14 at the interface of hippocampal signalling and synaptic plasticity. Trends in Pharmacological Sciences32(11):666-674. Abstract

Vellano CP, Shu FJ, Ramineni S, Yates CK, Tall GG, Hepler JR (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(5):752-62. Abstract

Lee, S.E., Simmons, S., Heldt, S.A., Schroeder, J.A, Zhao, M., Cowan, D.P., Vellano, C.P., Feng, Y., Weinshenker, D., Sweatt, D.L. 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, USA 107(39):16994-8.Abstract

Jernigan KK, Cselenyi CS, Thorne CA, Hanson AJ, Tahinci E, Hajicek N, Oldham WM, Lee LA, Hamm HE, Hepler JR, Kozasa T, Linder ME, Lee E (2010) Gbetagamma activates GSK3 to promote LRP6-mediated beta-catenin transcriptional activity. Science Signaling, 3(121):ra37. Abstract

McCoy, K.L., Traynelis, S.F. and Hepler, J.R. (2010) PAR1 and PAR2 couple to overlapping and distinct sets of G proteins and linked signaling pathways to regulate cell physiology.Molecular Pharmacology 77(6):1005-15. Abstract

Shu, F.J., Ramineni, S and Hepler, J.R. (2010) RGS14 is a multifunctional scaffold that integrates G protein and H-Ras/Raf/MAP kinase signaling pathways. Cellular Signalling22(3):366-76. PMID: 19878719. Abstract

McCoy, K.L., and Hepler, J.R. (2009) RGS proteins as central components of the G protein coupled receptor signaling complex.   Progress in Mol. Biol. Translational. Sci, 86; 49-74.Abstract

Pedone H. K., Bernstein, L.S., Linder, M.E., and Hepler, J.R. (2008) Measurement of protein palmitoylation. The Protein Protocols Handbook, Third Edition, Humana Press, (John Walker, Editor), pgs. 1613-1626. PDF file

Mannaioni, G., Goldshmidt, A., Hamill, C., Yuan, H., Pedone, K. H., Junge, C. E., Lee, C.J., Yepes, M., Hepler, J.R. , and Traynelis, S.F. (2008) Plasmin potentiates synaptic NMDA receptor function in rat hippocampal neurons through activation of PAR1. J. Biol. Chem.,  283(29): 20600-20611. Abstract

Pedone, K.H. and Hepler, J.R. (2007) The importance of amino terminal polycysteine and polybasic sequences  in  determining  G14α and G16α palmitoylation, plasma membrane targeting and signaling functions.  J. Biol. Chem.. 282: 25199-25212. Abstract

Gu, S., He, J., Ho, W.T., Ramineni, S., Thal D.M., Natesh, R., Tesmer, J.J.G., Hepler, J.R. and Heximer, S.P. (2007). Unique hydrophobic extension of the RGS2 amphipathic helix domain imparts increased plasma membrane binding and function relative to other RGS R4/B subfamily members. J. Biol. Chem., 282: 33064-75. Abstract

Shu F-J, Ramenini,S., Amyot, W.M., and Hepler, J.R.  (2007) Selective interactions between Giα1 and Giα3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization. Cellular Signalling, 17: 383-389. Abstract

Neitzel, K.L. and Hepler, J.R. (2006) Cellular mechanisms that determine selective regulation of G protein coupled receptor signaling by RGS proteins. Seminars in Developmental and Cellular Biology, 17: 383-389. Abstract

Roy, A.A., Baragli, A., Bernstein, L.S., Hepler, J.R., Hebert, T.E., and Chidiac, P. (2006) RGS2 interacts with adenylyl cyclase in living cells. Cellular Signalling., 18:336-48. Abstract

Hubbard, K.B and Hepler, J.R (2006) Cell signaling diversity of the Gqα family of heterotrimeric G proteins. Cellular Signalling, 18:135-50. Abstract

Hepler, JR. (2005) R7BP: A surprising new link between G proteins, RGS proteins and nuclear signaling in brain. Science STKE, 294, pe38. Abstract

Nicole, O., Sorensen, S.D., Sastre, A. Hepler, J.R.. Brat, D., McKeon, R.,  and Traynelis, S.F. (2005)  Activation of protease activated receptor-1 (PAR-1) contributes to glial scar formation after brain injury.  J. Neuroscience, 25, 4319-4329. Abstract

Hague, C., Bernstein, L.S., Ramenini,S., Chen, Z.J., Minneman, K.P. and Hepler, J.R. (2005) Selective inhibition of α_1A-adrenergic receptor signaling by RGS2 association with the receptor third intracellular loop. J .Biol Chem., 280, 27289-27295. Abstract

Peavy, R.B., Hubbard, K.B., Lau, A.G., Fields, B., Lee, T.T., Gernert, K., Murphy, T. J., and Hepler, J.R. (2005) Differential effects of Gqα, G14α and G15α on vascular smooth muscle cell survival and gene expression profiles. Molecular Pharmacology, 67:2102-14. Abstract

Hepler, J.R., Cladman, W. Ramenini, S. Hollinger, S. and Chidiac, P. (2005) Novel activity of RGS14 on Goα and Giα nucleotide binding and hydrolysis independent of its RGS domain and GDI activity.  Biochemistry, 44, 5495-5502. Abstract

Bernstein, L.S., Ramineni, S., Chris Hague, Wendy Cladman, Peter Chidiac, Levey, A.I. and Hepler, J.R.  (2004) RGS2 binds directly and selectively to the M1 muscarinic cholinergic receptor third intracellular loop to modulate Gq/11α signaling.J. Biol. Chem., 279, 21248-21256. Abstract

Bernstein, L.S., Linder, M.E. and Hepler, J.R. (2004)  Analysis of RGS protein palmitoylation. Meth. Mol. Biol.. 237, 195-204. Abstract

Hollinger, S. and Hepler, J.R. (2004) Methods for measuring phosphorylation of RGS proteins by G protein regulated kinases. Meth. Mol. Biol., 237, 205-219. Abstract

Junge, C.E., Lee, J.C, Hubbard, K.B., Zhang, Z., Olsen, J.J., Hepler, J.R., Brat, D.J., Traynelis, S.F. (2004) Protease activated receptor-1 (PAR-1) in human brain: localization and functional expression in astrocytes. Experimental Neurology, 188, 94-103. Abstract

Hepler, J.R. (2003) RGS protein and G protein interactions: A little help from their friends.Molecular Pharmacology., 64, 547-549. Abstract

Hollinger, S., Ramineni, S., and Hepler, J.R. (2003) Phosphorylation of RGS14 by protein kinase A modulates its activity toward Gαi, Biochemistry, 42, 811-819. Abstract

Sorensen, S.D., Nicole, O., Peavy, R.D., Montoya, L.M., Lee, J.C., Murphy, T.J., Traynelis, S.,F. and Hepler, J.R. (2003) Common signaling pathways link activation of murine PAR-1, LPA and S1P receptors to proliferation of astrocytes.Molecular Pharmacology., 64, 1199-1209. Abstract

Hollinger, S. and Hepler, J.R. (2002) Cellular roles and regulation of RGS proteins: modulators and integrators of G protein signaling Pharmacological Reviews, 54(3), 527-559. Abstract

Hollinger, S., Taylor, J.B.,  Hoag-Goldman, E.M., 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. Abstract

Cunningham, M.L., Waldo, G.L., Hollinger, S.,  Hepler, J.R. and Harden, T.K. (2001) PKC phosphorylates RGS2 and modulates its capacity for negative regulation of Gα11 signaling.J. Biol. Chem., 276, 5438-5444. Abstract

Chidiac, P., Gadd, M.E. and Hepler, J.R.  (2001) Methods for measuring RGS interactions wit Gqα. Methods  Enzymol., 344(B), 686-702. Abstract

Rose, J.J., Taylor, J.B., Shi, J., Jones, P.G, Cockett, M.R. and Hepler, J.R. (2000) RGS7 is palmitoylated and exists as biochemically distinct populations. J. Neurochem., 75, 2103-2112. Abstract

Heximer, S. P., Srinivasa, S.P., Bernstein, L.S., Bernard, J.L., Linder, M.E., Hepler, J.R. and  Blumer, K.J. (1999) G protein selectivity is a determinant of RGS2 function. J. Biol. Chem., 274, 34253-34259. Abstract

Hepler, J.R. (1999) Emerging roles for RGS proteins in cell signaling. Trends Pharmacol. Sci. 20, 376-382. Abstract

Saugstad, J.A., Marino, M.J., Folk, J.A., Hepler, J.R. and Conn, P.J.  (1998)  RGS4 inhibits signaling by group I metabotropic glutamate receptors.  J. Neuroscience 18, 905-913. Abstract

Heximer, S.P., Watson, N., Linder, M.E., Blumer, K.J. and Hepler, J.R. (1997) RGS2/GOS8 is a selective inhibitor of Gqα function.  Proc. Natl. Acad. Sci. USA 94, 14389-14393. Abstract

Hepler, J.R., Berman, D.M., Gilman, A.G. and Kozasa, T. (1997) RGS4 and GAIP are GAPs for Gqα and block activation of phospholipase Cβ by GTPγS-Gqα. Proc. Natl. Acad. Sci. USA 94: 428-432. Abstract

Huang C, Hepler JR, Gilman AG, Mumby SM. (1997) Attenuation of Gi- and Gq-mediated signaling by expression of RGS4 or GAIP in mammalian cells.  Proc. Natl. Acad. Sci US, Jun 10; 94(12): 6159-63. Abstract

Huang C, Hepler JR, Chen LT, Gilman AG, Anderson RG, Mumby SM (1997) Organization of G proteins and adenylyl cyclase at the plasma membrane. Mol Biol Cell. Dec 8 (12): 2365-78. Abstract

Hepler, J.R., Biddlecome, G.H., Kleuss, C., Camp, L.A., Hofmann, S.L., Ross, E.M. and Gilman, A.G. (1996) Functional importance of the amino terminus of Gqα.  J. Biol. Chem. 271, 496-504. Abstract

Taussig, R., Tang, W.-J., Hepler, J.R. and Gilman, A.G. (1994) Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases. J. Biol. Chem. 269, 6093-6100. Abstract

Hepler, J.R., Kozasa, T. and Gilman, A.G. (1994) Purification of recombinant Gqα, G11α, and G16α from Sf9 cells. Meth. Enzymol. 237, 191-212. Abstract

Kozasa, T., Hepler, J.R., Smrcka, A.V., Simon, M.I., Rhee, S.G., Sternweis, P.C. and Gilman, A.G. (1993) Purification and characterization of recombinant G16 from Sf9 cells: Activation of purified phospholipase C isozymes by G-protein subunits. Proc. Natl. Acad. Sci. USA 90, 9176-9180. Abstract

Hepler, J.R., Kozasa, T., Smrcka, A.V., Simon, M.I., Rhee, S.G., Sternweis, P.C. and Gilman, A.G. (1993) Purification from Sf9 cells and characterization of recombinant Gqα and G11α.  Activation of purified phospholipase Cβ isozymes by Gα subunits.   J. Biol. Chem. 268: 14367-14375. Abstract

Linder, M.E., Middleton, P., Hepler, J.R., Taussig, R., Gilman, A.G. and Mumby, S.M. (1993) Lipid modifications of G proteins: subunits are palmitoylated. Proc. Natl. Acad. Sci. U.S.A. 90, 3675-3679. Abstract

Hepler, J.R. and Gilman, A.G. (1992) G Proteins. Trends Biochem. Sci. 17, 383-387.Abstract

Smrcka, A.V., Hepler, J.R., Brown, K.O., Sternweis, P.C. (1991) Purified Gq regulates polyphosphoinositide-specific phospholipase C activity.  Science 251, 804-807. Abstract

Hepler, J.R., Jeffs, R.A., Huckle, W.R., Outlaw, H.E., Rhee, S.G., Earp, H.S. and Harden, T.K. (1990) Evidence that the epidermal growth factor and non-tyrosine kinase hormone receptors stimulate phosphoinositide hydrolysis by independent pathways.  Biochem. J.270, 337-344. Abstract

Hepler, J.R., Earp, H.S. and Harden, T.K. (1988) Long-term phorbol ester treatment down-regulates protein kinase C (PKC) and sensitizes the phosphoinositide signalling system to hormone and growth factor stimulation: Evidence for a role of PKC in agonist-induced desensitization. J. Biol. Chem. 263, 7610-7619. Abstract

Hepler, J.R., Nakahata, N., Lovenberg, T.W., DiGuiseppi, J., Herman, B., Earp, H.S. and Harden, T.K. (1987) Epidermal growth factor stimulates the rapid accumulation of inositol (1,4,5) trisphosphate and a rise in cytosolic calcium-mobilized from intracellular stores in A431 cells. J. Biol. Chem. 262, 2951-2956. Abstract

Hepler, J.R. and Harden, T.K. (1986) Guanine nucleotide-dependent, pertussis toxin-insensitive stimulation of inositol phosphate formation by carbachol in a membrane preparation from human astrocytoma cells. Biochem. J. 239, 141-146. Abstract

Nakahata N, Martin MW, Hughes AR, Hepler JR, Harden TK (1986) H1-Histamine receptors on human astrocytoma cells. Mol Pharmacol. 1986 Feb;29 (2): 188-95. Abstract

Evans T, Hepler JR, Masters SB, Brown JH, Harden TK. (1985) Guanine nucleotide regulation of agonist binding to muscarinic cholinergic receptors. Relation to efficacy of agonists and for stimulation of phosphoinositide breakdown and calcium mobilization. Biochem J.  Dec 15; 232(3): 751-7. Abstract