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G protein effectors

G protein effectors. Maria Diverse-Pierluissi, Ph.D. Department of Pharmacology and Biological Chemistry Mount Sinai School of Medicine. February 11, 2005. Regulation of G-protein-mediated signals. Regulation of receptor-G protein coupling. 1-Receptor phosphorylation 2-GTP hydrolysis.

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G protein effectors

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  1. G protein effectors Maria Diverse-Pierluissi, Ph.D. Department of Pharmacology and Biological Chemistry Mount Sinai School of Medicine February 11, 2005

  2. Regulation of G-protein-mediated signals

  3. Regulation of receptor-G protein coupling 1-Receptor phosphorylation 2-GTP hydrolysis

  4. G protein-coupled receptor kinases (GRKs) A family of serine-threonine kinases that recognizes and phosphorylates receptors in their agonist-stimulated form. Consensus sequence: serine/threonine residues surrounded by acidic residues DLEESSSSD

  5. Receptor phosphorylation by second messenger kinases Receptor phosphorylation by GRKs Receptor phosphorylation

  6. Members of the GRK family and their regulation

  7. Mechanisms of GPCR regulation by GRKs and arrestin Kohout TA, Lefkowitz RJ. Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization. Mol Pharmacol. 2003 Jan;63(1):9-18.

  8. Regulation of GRK function Penela P, Ribas C, Mayor F. Jr. Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases. Cell Signal. 2003 Nov;15(11):973-981.

  9. Phenotypes of GRK and arrestin knockout mice Kohout TA, Lefkowitz RJ. Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization. Mol Pharmacol. 2003 Jan;63(1):9-18.

  10. Other GRK substrates Tubulin Synuclein Phosducin

  11. Fukuto HS, Ferkey DM, Apicella AJ, Lans H, Sharmeen T, Chen W, Lefkowitz RJ, Jansen G, Schafer WR, Hart AC. G protein-coupled receptor kinase function is essential for chemosensation in C. elegans. Neuron. 2004 May;42(4):581-593.

  12. Fong AM, Premont RT, Richardson RM, Yu YR, Lefkowitz RJ, Patel DD. Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7478-7483.

  13. Fong AM, Premont RT, Richardson RM, Yu YR, Lefkowitz RJ, Patel DD. Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7478-7483.

  14. RGS proteins RGS proteins accelerate the rate of GTP hydrolysis. All members of the family share a 120 aa domain that binds to the active alpha subunit. First reports from yeast and C. elegans

  15. RGS6, RGS7, RGS9, RGS11

  16. Martin-McCaffrey L, Willard FS, Oliveira-dos-Santos AJ, Natale DR, Snow BE, Kimple RJ, Pajak A, Watson AJ, Dagnino L, Penninger JM, Siderovski DP, D'Souza SJ. RGS14 is a mitotic spindle protein essential from the first division of the mammalian zygote. Dev Cell. 2004 Nov;7(5):763-769.

  17. Martin-McCaffrey L, Willard FS, Oliveira-dos-Santos AJ, Natale DR, Snow BE, Kimple RJ, Pajak A, Watson AJ, Dagnino L, Penninger JM, Siderovski DP, D'Souza SJ. RGS14 is a mitotic spindle protein essential from the first division of the mammalian zygote. Dev Cell. 2004 Nov;7(5):763-769.

  18. Four Dutch patients had a missense mutationW299R in the RGS9 gene The mutation destabilizes the structure, resulting in a decrease in the catalytic activity of RGS9 Nishiguchi KM, Sandberg MA, Kooijman AC, Martemyanov KA, Pott JW, Hagstrom SA, Arshavsky VY, Berson EL, Dryja TP. Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation. Nature. 2004 Jan 1;427(6969):75-78.

  19. Tyrosine kinase-dependent recruitment of RGS12 to N-type calcium channel Schiff ML, Siderovski DP, Jordan JD, Brothers G, Snow B, De Vries L, Ortiz DF, Diverse-Pierluissi M. Tyrosine-kinase-dependent recruitment of RGS12 to the N-type calcium channel. Nature. 2000 Dec 7;408(6813):723-727.

  20. Binding of RGS12 to the tyrosine 804 motif in the SNARE-binding (synprint) site of the Cav2.2 channel Richman RW, Strock J, Hains MD, Cabanilla NJ, Lau KK, Siderovski DP, Diverse-Pierluissi M. RGS12 interacts with the SNARE-binding region of the Cav2.2 calcium channel. J Biol Chem. 2005 Jan 14;280(2):1521-1528.

  21. G protein effectors

  22. Differential regulation of the different types of adenylyl cyclase Jordan JD, Landau EM, Iyengar R.Signaling networks: the origins of cellular multitasking. Cell. 2000 Oct 13;103(2):193-200.

  23. Isoforms of mammalian adenylyl cyclase Sunahara RK, Taussig R. Isoforms of mammalian adenylyl cyclase: multiplicities of signaling.Mol Interv. 2002 Jun;2(3):168-184.

  24. Isoformsof mammalian adenylyl cyclase Sunahara RK, Taussig R. Isoforms of mammalian adenylyl cyclase: multiplicities of signaling. Mol Interv. 2002 Jun;2(3):168-184.

  25. Phospholipase C family Wing MR, Bourdon DM, Harden TK. PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling. Mol Interv. 2003 Aug;3(5):273-280.

  26. Regulation of phospholipase C by Gq- and Gi-coupled receptors

  27. Regulation of Phospholipase C-epsilon Wing MR, Bourdon DM, Harden TK. PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling. Mol Interv. 2003 Aug;3(5):273-280.

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