HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, C. Articles by Lin, S.-C. Search for Related Content PubMed PubMed Citation Articles by Chen, C. Articles by Lin, S.-C. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 28, 19799-19806, July 9, 1999

The Membrane Association Domain of RGS16 Contains Unique Amphipathic Features That Are Conserved in RGS4 and RGS5

From the Regulatory Biology Laboratory, Institute of Molecular and Cell Biology, National University of Singapore, 30 Medical Drive, Singapore 117609, Republic of Singapore

Regulators of G protein signaling (RGS proteins) modulate G protein-mediated signaling pathways by acting as GTPase-activating proteins for G_i, G_q, and G₁₂ -subunits of heterotrimeric G proteins. Although it is known that membrane association is critical for the biological activities of many RGS proteins, the mechanism underlying this requirement remains unclear. We reported recently that the NH₂ terminus of RGS16 is required for its function in vivo. In this study, we show that RGS16 lacking the NH₂ terminus is no longer localized to the plasma membrane as is the wild type protein, suggesting that membrane association is important for biological function. The region of amino acids 7-32 is sufficient to confer the membrane-targeting activity, of which amino acids 12-30 are predicted to adopt an amphipathic -helix. Site-directed mutagenesis experiments showed that the hydrophobic residues of the nonpolar face of the helix and the strips of positively charged side chains positioned along the polar/nonpolar interface of the helix are crucial for membrane association. Subcellular fractionation by differential centrifugation followed by conditions that distinguish peripheral membrane proteins from integral ones indicate that RGS16 is a peripheral membrane protein. We show further that RGS16 membrane association does not require palmitoylation. Our results, together with other recent findings, have defined a unique membrane association domain with amphipathic features. We believe that these structural features and the mechanism of membrane association of RGS16 are likely to apply to the homologous domains in RGS4 and RGS5.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. H. Nisancioglu, W. M. Mahoney Jr., D. D. Kimmel, S. M. Schwartz, C. Betsholtz, and G. Genove Generation and Characterization of rgs5 Mutant Mice Mol. Cell. Biol., April 1, 2008; 28(7): 2324 - 2331. [Abstract] [Full Text] [PDF]

				S. Gu, J. He, W.-T. Ho, S. Ramineni, D. M. Thal, R. Natesh, J. J. G. Tesmer, J. R. Hepler, and S. P. Heximer 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., November 9, 2007; 282(45): 33064 - 33075. [Abstract] [Full Text] [PDF]

				K. H. Pedone and J. R. Hepler The Importance of N-terminal Polycysteine and Polybasic Sequences for G14{alpha} and G16{alpha} Palmitoylation, Plasma Membrane Localization, and Signaling Function J. Biol. Chem., August 31, 2007; 282(35): 25199 - 25212. [Abstract] [Full Text] [PDF]

				C. Toro-Castillo, A. Thapliyal, H. Gonzalez-Ochoa, B. A. Adams, and U. Meza Muscarinic modulation of Cav2.3 (R-type) calcium channels is antagonized by RGS3 and RGS3T Am J Physiol Cell Physiol, January 1, 2007; 292(1): C573 - C580. [Abstract] [Full Text] [PDF]

				C. Jaen and C. A. Doupnik RGS3 and RGS4 Differentially Associate with G Protein-coupled Receptor-Kir3 Channel Signaling Complexes Revealing Two Modes of RGS Modulation: PRECOUPLING AND COLLISION COUPLING J. Biol. Chem., November 10, 2006; 281(45): 34549 - 34560. [Abstract] [Full Text] [PDF]

				Y. Le, M. Honczarenko, A. M. Glodek, D. K. Ho, and L. E. Silberstein CXC Chemokine Ligand 12-Induced Focal Adhesion Kinase Activation and Segregation into Membrane Domains Is Modulated by Regulator of G Protein Signaling 1 in Pro-B Cells J. Immunol., March 1, 2005; 174(5): 2582 - 2590. [Abstract] [Full Text] [PDF]

				D. T. Dinh, H. Qian, R. Seeber, E. Lim, K. Pfleger, K. A. Eidne, and W. G. Thomas Helix I of {beta}-Arrestin Is Involved in Postendocytic Trafficking but Is Not Required for Membrane Translocation, Receptor Binding, and Internalization Mol. Pharmacol., February 1, 2005; 67(2): 375 - 382. [Abstract] [Full Text] [PDF]

				H. Cho, D.-U. Kim, and J. H. Kehrl RGS14 Is a Centrosomal and Nuclear Cytoplasmic Shuttling Protein That Traffics to Promyelocytic Leukemia Nuclear Bodies Following Heat Shock J. Biol. Chem., January 7, 2005; 280(1): 805 - 814. [Abstract] [Full Text] [PDF]

				Y. Zhu, B. J. Swanson, M. Wang, D. A. Hildeman, B. C. Schaefer, X. Liu, H. Suzuki, K. Mihara, J. Kappler, and P. Marrack Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells PNAS, May 18, 2004; 101(20): 7681 - 7686. [Abstract] [Full Text] [PDF]

				L. Zhang, J. Lin, and G. Ji Membrane Anchoring of the AgrD N-terminal Amphipathic Region Is Required for Its Processing to Produce a Quorum-sensing Pheromone in Staphylococcus aureus J. Biol. Chem., May 7, 2004; 279(19): 19448 - 19456. [Abstract] [Full Text] [PDF]

				M. M. Thiyagarajan, R. P. Stracquatanio, A. N. Pronin, D. S. Evanko, J. L. Benovic, and P. B. Wedegaertner A Predicted Amphipathic Helix Mediates Plasma Membrane Localization of GRK5 J. Biol. Chem., April 23, 2004; 279(17): 17989 - 17995. [Abstract] [Full Text] [PDF]

				T. Anger, W. Zhang, and U. Mende Differential Contribution of GTPase Activation and Effector Antagonism to the Inhibitory Effect of RGS Proteins on Gq-mediated Signaling in Vivo J. Biol. Chem., February 6, 2004; 279(6): 3906 - 3915. [Abstract] [Full Text] [PDF]

				B. Ma, G. Wang, M. M. Palcic, B. Hazes, and D. E. Taylor C-terminal Amino Acids of Helicobacter pylori{alpha}1,3/4 Fucosyltransferases Determine Type I and Type II Transfer J. Biol. Chem., June 6, 2003; 278(24): 21893 - 21900. [Abstract] [Full Text] [PDF]

				A. Hiol, P. C. Davey, J. L. Osterhout, A. A. Waheed, E. R. Fischer, C.-K. Chen, G. Milligan, K. M. Druey, and T. L. Z. Jones Palmitoylation Regulates Regulators of G-protein Signaling (RGS) 16 Function: I. MUTATION OF AMINO-TERMINAL CYSTEINE RESIDUES ON RGS16 PREVENTS ITS TARGETING TO LIPID RAFTS AND PALMITOYLATION OF AN INTERNAL CYSTEINE RESIDUE J. Biol. Chem., May 23, 2003; 278(21): 19301 - 19308. [Abstract] [Full Text] [PDF]

				J. L. Osterhout, A. A. Waheed, A. Hiol, R. J. Ward, P. C. Davey, L. Nini, J. Wang, G. Milligan, T. L. Z. Jones, and K. M. Druey Palmitoylation Regulates Regulator of G-protein Signaling (RGS) 16 Function: II. PALMITOYLATION OF A CYSTEINE RESIDUE IN THE RGS BOX IS CRITICAL FOR RGS16 GTPase ACCELERATING ACTIVITY AND REGULATION OF Gi-COUPLED SIGNALING J. Biol. Chem., May 23, 2003; 278(21): 19309 - 19316. [Abstract] [Full Text] [PDF]

				Y.-S. Ouyang, Y. Tu, S. A. Barker, and F. Yang Regulators of G-protein Signaling (RGS) 4, Insertion into Model Membranes and Inhibition of Activity by Phosphatidic Acid J. Biol. Chem., March 21, 2003; 278(13): 11115 - 11122. [Abstract] [Full Text] [PDF]

				P. Tosetti, T. Turner, Q. Lu, and K. Dunlap Unique Isoform of Galpha -interacting Protein (RGS-GAIP) Selectively Discriminates between Two Go-mediated Pathways That Inhibit Ca2+ Channels J. Biol. Chem., November 22, 2002; 277(48): 46001 - 46009. [Abstract] [Full Text] [PDF]

				P. J. Welsby, E. Kellett, G. Wilkinson, and G. Milligan Enhanced Detection of Receptor Constitutive Activity in the Presence of Regulators of G Protein Signaling: Applications to the Detection and Analysis of Inverse Agonists and Low-Efficacy Partial Agonists Mol. Pharmacol., May 1, 2002; 61(5): 1211 - 1221. [Abstract] [Full Text] [PDF]

				C. Castro-Fernandez, J. A. Janovick, S. P. Brothers, R. A. Fisher, T. H. Ji, and P. M. Conn Regulation of RGS3 and RGS10 Palmitoylation by GnRH Endocrinology, April 1, 2002; 143(4): 1310 - 1317. [Abstract] [Full Text] [PDF]

				A. Derrien and K. M. Druey RGS16 Function Is Regulated by Epidermal Growth Factor Receptor-mediated Tyrosine Phosphorylation J. Biol. Chem., December 14, 2001; 276(51): 48532 - 48538. [Abstract] [Full Text] [PDF]

				L. D. Adams, R. L. Geary, B. McManus, and S. M. Schwartz A Comparison of Aorta and Vena Cava Medial Message Expression by cDNA Array Analysis Identifies a Set of 68 Consistently Differentially Expressed Genes, All in Aortic Media Circ. Res., September 29, 2000; 87(7): 623 - 631. [Abstract] [Full Text] [PDF]

				B. C. Low, K. T. Seow, and G. R. Guy Evidence for a Novel Cdc42GAP Domain at the Carboxyl Terminus of BNIP-2 J. Biol. Chem., May 5, 2000; 275(19): 14415 - 14422. [Abstract] [Full Text] [PDF]

				B. Zheng, D. Chen, and M. G. Farquhar MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16 PNAS, April 11, 2000; 97(8): 3999 - 4004. [Abstract] [Full Text] [PDF]

				T. Fischer, E. Elenko, L. Wan, G. Thomas, and M. G. Farquhar Membrane-associated GAIP is a phosphoprotein and can be phosphorylated by clathrin-coated vesicles PNAS, April 11, 2000; 97(8): 4040 - 4045. [Abstract] [Full Text] [PDF]

				Y. Tu, S. Popov, C. Slaughter, and E. M. Ross 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., December 31, 1999; 274(53): 38260 - 38267. [Abstract] [Full Text] [PDF]

				L. S. Bernstein, A. A. Grillo, S. S. Loranger, and M. E. Linder RGS4 Binds to Membranes through an Amphipathic alpha -Helix J. Biol. Chem., June 9, 2000; 275(24): 18520 - 18526. [Abstract] [Full Text] [PDF]

				S. G. Popov, U. M. Krishna, J. R. Falck, and T. M. Wilkie Ca2+/Calmodulin Reverses Phosphatidylinositol 3,4,5-Trisphosphate-dependent Inhibition of Regulators of G Protein-signaling GTPase-activating Protein Activity J. Biol. Chem., June 16, 2000; 275(25): 18962 - 18968. [Abstract] [Full Text] [PDF]

				B. C. Low, K. T. Seow, and G. R. Guy The BNIP-2 and Cdc42GAP Homology Domain of BNIP-2 Mediates Its Homophilic Association and Heterophilic Interaction with Cdc42GAP J. Biol. Chem., November 22, 2000; 275(48): 37742 - 37751. [Abstract] [Full Text] [PDF]

				I.-K. Park, C. A. Klug, K. Li, L. Jerabek, L. Li, M. Nanamori, R. R. Neubig, L. Hood, I. L. Weissman, and M. F. Clarke Molecular Cloning and Characterization of a Novel Regulator of G-protein Signaling from Mouse Hematopoietic Stem Cells J. Biol. Chem., January 5, 2001; 276(2): 915 - 923. [Abstract] [Full Text] [PDF]

				O. Saitoh, I. Masuho, I. Terakawa, S. Nomoto, T. Asano, and Y. Kubo Regulator of G Protein Signaling 8 (RGS8) Requires Its NH2 Terminus for Subcellular Localization and Acute Desensitization of G Protein-gated K+ Channels J. Biol. Chem., February 9, 2001; 276(7): 5052 - 5058. [Abstract] [Full Text] [PDF]

				S. P. Heximer, H. Lim, J. L. Bernard, and K. J. Blumer Mechanisms Governing Subcellular Localization and Function of Human RGS2 J. Biol. Chem., April 20, 2001; 276(17): 14195 - 14203. [Abstract] [Full Text] [PDF]

				Y. Tu, J. Woodson, and E. M. Ross Binding of Regulator of G Protein Signaling (RGS) Proteins to Phospholipid Bilayers. CONTRIBUTION OF LOCATION AND/OR ORIENTATION TO GTPase-ACTIVATING PROTEIN ACTIVITY J. Biol. Chem., June 1, 2001; 276(23): 20160 - 20166. [Abstract] [Full Text] [PDF]

				W. He, T. J. Melia, C. W. Cowan, and T. G. Wensel Dependence of RGS9-1 Membrane Attachment on Its C-terminal Tail J. Biol. Chem., December 21, 2001; 276(52): 48961 - 48966. [Abstract] [Full Text] [PDF]

				N. O. Dulin, P. Pratt, C. Tiruppathi, J. Niu, T. Voyno-Yasenetskaya, and M. J. Dunn Regulator of G Protein Signaling RGS3T Is Localized to the Nucleus and Induces Apoptosis J. Biol. Chem., July 7, 2000; 275(28): 21317 - 21323. [Abstract] [Full Text] [PDF]

				M. E. Sowa, W. He, T. G. Wensel, and O. Lichtarge A regulator of G protein signaling interaction surface linked to effector specificity PNAS, February 15, 2000; 97(4): 1483 - 1488. [Abstract] [Full Text] [PDF]