|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 20, 12316-12324, May 15, 1998
From the Howard Hughes Medical Institute Laboratories and
Departments of Medicine and Biochemistry, The G protein-coupled receptor kinase 2 (GRK2) is
a serine/threonine kinase that phosphorylates and desensitizes
agonist-occupied G protein-coupled receptors (GPCRs). Here we
demonstrate that GRK2 is a microtubule-associated protein and
identify tubulin as a novel GRK2 substrate. GRK2 is associated with
microtubules purified from bovine brain, forms a complex with tubulin
in cell extracts, and colocalizes with tubulin in living cells.
Furthermore, an endogenous tubulin kinase activity that copurifies with
microtubules has properties similar to GRK2 and is inhibited by
anti-GRK2 monoclonal antibodies. Indeed, GRK2 phosphorylates tubulin
in vitro with kinetic parameters very similar to those for
phosphorylation of the agonist-occupied
The G Protein-coupled Receptor Kinase 2 Is a
Microtubule-associated Protein Kinase That Phosphorylates Tubulin
,,,
Cell Biology,
and ¶ Microbiology, Duke University Medical Center,
Durham, North Carolina 27710
2-adrenergic
receptor, suggesting a functionally relevant role for this
phosphorylation event. In a cellular environment, agonist occupancy of
GPCRs, which leads to recruitment of GRK2 to the plasma membrane and
its subsequent activation, promotes GRK2-tubulin complex formation and
tubulin phosphorylation. These findings suggest a novel role for GRK2
as a GPCR signal transducer mediating the effects of GPCR activation on
the cytoskeleton.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. H. A. Nijboer, A. Kavelaars, A. Vroon, F. Groenendaal, F. van Bel, and C. J. Heijnen Low Endogenous G-Protein-Coupled Receptor Kinase 2 Sensitizes the Immature Brain to Hypoxia-Ischemia-Induced Gray and White Matter Damage J. Neurosci., March 26, 2008; 28(13): 3324 - 3332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Harris, H. I. Cohn, S. Pesant, R.-H. Zhou, and A. D. Eckhart Vascular smooth muscle Gq signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3072 - H3079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lattin, D. A. Zidar, K. Schroder, S. Kellie, D. A. Hume, and M. J. Sweet G-protein-coupled receptor expression, function, and signaling in macrophages J. Leukoc. Biol., July 1, 2007; 82(1): 16 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ruiz-Gomez, B. Mellstrom, D. Tornero, E. Morato, M. Savignac, H. Holguin, K. Aurrekoetxea, P. Gonzalez, C. Gonzalez-Garcia, V. Cena, et al. G Protein-coupled Receptor Kinase 2-mediated Phosphorylation of Downstream Regulatory Element Antagonist Modulator Regulates Membrane Trafficking of Kv4.2 Potassium Channel J. Biol. Chem., January 12, 2007; 282(2): 1205 - 1215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vroon, C. J. Heijnen, and A. Kavelaars GRKs and arrestins: regulators of migration and inflammation J. Leukoc. Biol., December 1, 2006; 80(6): 1214 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Neve Novel Features of G Protein-Coupled Receptor Kinase 4 Mol. Pharmacol., March 1, 2006; 69(3): 673 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Kenski, C. Zhang, M. von Zastrow, and K. M. Shokat Chemical Genetic Engineering of G Protein-coupled Receptor Kinase 2 J. Biol. Chem., October 14, 2005; 280(41): 35051 - 35061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Cant and J. A. Pitcher G Protein-coupled Receptor Kinase 2-mediated Phosphorylation of Ezrin Is Required for G Protein-coupled Receptor-dependent Reorganization of the Actin Cytoskeleton Mol. Biol. Cell, July 1, 2005; 16(7): 3088 - 3099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Chang, S.-K. Kim, T.-K. Kwon, S. S. Bae, D. S. Min, Y. H. Lee, S.-O. Kim, J.-K. Seo, J. H. Choi, and P.-G. Suh Pleckstrin Homology Domains of Phospholipase C-{gamma}1 Directly Interact with {beta}-Tubulin for Activation of Phospholipase C-{gamma}1 and Reciprocal Modulation of {beta}-Tubulin Function in Microtubule Assembly J. Biol. Chem., February 25, 2005; 280(8): 6897 - 6905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Gan, Z. Ma, N. Deng, J. Wang, J. Ding, and L. Li Involvement of the C-terminal Proline-rich Motif of G Protein-coupled Receptor Kinases in Recognition of Activated Rhodopsin J. Biol. Chem., November 26, 2004; 279(48): 49741 - 49746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Chen, R. Gaudreau, C. Le Gouill, M. Rola-Pleszczynski, and J. Stankova Agonist-Induced Internalization of Leukotriene B4 Receptor 1 Requires G-Protein-Coupled Receptor Kinase 2 but Not Arrestins Mol. Pharmacol., September 1, 2004; 66(3): 377 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vroon, C. J. Heijnen, M. S. Lombardi, P. M. Cobelens, F. Mayor Jr, M. G. Caron, and A. Kavelaars Reduced GRK2 level in T cells potentiates chemotaxis and signaling in response to CCL4 J. Leukoc. Biol., May 1, 2004; 75(5): 901 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Luo and J. L. Benovic G Protein-coupled Receptor Kinase Interaction with Hsp90 Mediates Kinase Maturation J. Biol. Chem., December 19, 2003; 278(51): 50908 - 50914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Olivera, H. M. Rosenfeldt, M. Bektas, F. Wang, I. Ishii, J. Chun, S. Milstien, and S. Spiegel Sphingosine Kinase Type 1 Induces G12/13-mediated Stress Fiber Formation, yet Promotes Growth and Survival Independent of G Protein-coupled Receptors J. Biol. Chem., November 21, 2003; 278(47): 46452 - 46460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Miller, D. A. Houtz, C. D. Nelson, P. E. Kolattukudy, and R. J. Lefkowitz G-protein-coupled Receptor (GPCR) Kinase Phosphorylation and {beta}-Arrestin Recruitment Regulate the Constitutive Signaling Activity of the Human Cytomegalovirus US28 GPCR J. Biol. Chem., June 6, 2003; 278(24): 21663 - 21671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. SARMA, T. VOYNO-YASENETSKAYA, T. J. HOPE, and M. M. RASENICK Heterotrimeric G-proteins associate with microtubules during differentiation in PC12 pheochromocytoma cells FASEB J, May 1, 2003; 17(8): 848 - 859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang and X. J. Liu A G Protein-coupled Receptor Kinase Induces Xenopus Oocyte Maturation J. Biol. Chem., April 25, 2003; 278(18): 15809 - 15814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sterne-Marr, J. J. G. Tesmer, P. W. Day, R. P. Stracquatanio, J.-A. E. Cilente, K. E. O'Connor, A. N. Pronin, J. L. Benovic, and P. B. Wedegaertner G Protein-coupled Receptor Kinase 2/Galpha q/11 Interaction. A NOVEL SURFACE ON A REGULATOR OF G PROTEIN SIGNALING HOMOLOGY DOMAIN FOR BINDING Galpha SUBUNITS J. Biol. Chem., February 14, 2003; 278(8): 6050 - 6058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Pao and J. L. Benovic Phosphorylation-Independent Desensitization of G Protein-Coupled Receptors? Sci. Signal., October 8, 2002; 2002(153): pe42 - pe42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Donati, C. Thukral, and M. M. Rasenick Chronic Treatment of C6 Glioma Cells with Antidepressant Drugs Results in a Redistribution of Gsalpha Mol. Pharmacol., June 1, 2001; 59(6): 1426 - 1432. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. G. I. Khoo and F. Y. T. Sin Molecular cloning and characterisation of a novel membrane receptor gene from the lobster Jasus edwardsii J. Exp. Biol., January 10, 2001; 204(19): 3369 - 3377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Koide, M. Hamawaki, T. Narishige, H. Sato, S. Nemoto, G. DeFreyte, M. R. Zile, G. Cooper IV, and B. A. Carabello Microtubule Depolymerization Normalizes In Vivo Myocardial Contractile Function in Dogs With Pressure-Overload Left Ventricular Hypertrophy Circulation, August 29, 2000; 102(9): 1045 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Popova and M. M. Rasenick Muscarinic Receptor Activation Promotes the Membrane Association of Tubulin for the Regulation of Gq-Mediated Phospholipase Cbeta 1 Signaling J. Neurosci., April 15, 2000; 20(8): 2774 - 2782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Carman, L. S. Barak, C. Chen, L.-Y. Liu-Chen, J. J. Onorato, S. P. Kennedy, M. G. Caron, and J. L. Benovic Mutational Analysis of Gbeta gamma and Phospholipid Interaction with G Protein-coupled Receptor Kinase 2 J. Biol. Chem., March 31, 2000; 275(14): 10443 - 10452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Santini, R. Penn, A. Gagnon, J. Benovic, and J. Keen Selective recruitment of arrestin-3 to clathrin coated pits upon stimulation of G protein-coupled receptors J. Cell Sci., January 7, 2000; 113(13): 2463 - 2470. [Abstract] [PDF]
|
|
|
|
|
|
J. A. Pitcher, J. J. G. Tesmer, J. L. R. Freeman, W. D. Capel, W. C. Stone, and R. J. Lefkowitz Feedback Inhibition of G Protein-coupled Receptor Kinase 2 (GRK2) Activity by Extracellular Signal-regulated Kinases J. Biol. Chem., December 3, 1999; 274(49): 34531 - 34534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sarnago, A. Elorza, and F. Mayor Jr. Agonist-dependent Phosphorylation of the G Protein-coupled Receptor Kinase 2 (GRK2) by Src Tyrosine Kinase J. Biol. Chem., November 26, 1999; 274(48): 34411 - 34416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Carman, J.-L. Parent, P. W. Day, A. N. Pronin, P. M. Sternweis, P. B. Wedegaertner, A. G. Gilman, J. L. Benovic, and T. Kozasa Selective Regulation of Galpha q/11 by an RGS Domain in the G Protein-coupled Receptor Kinase, GRK2 J. Biol. Chem., November 26, 1999; 274(48): 34483 - 34492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Timm, B. Titus, K. Bernd, and M. Barroso The EF-hand Ca2+-binding Protein p22 Associates with Microtubules in an N-Myristoylation-dependent Manner Mol. Biol. Cell, October 1, 1999; 10(10): 3473 - 3488. [Abstract] [Full Text]
|
|
|
|
|
|
R. A. Hall, R. F. Spurney, R. T. Premont, N. Rahman, J. T. Blitzer, J. A. Pitcher, and R. J. Lefkowitz G Protein-coupled Receptor Kinase 6A Phosphorylates the Na+/H+ Exchanger Regulatory Factor via a PDZ Domain-mediated Interaction J. Biol. Chem., August 20, 1999; 274(34): 24328 - 24334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Hall, R. T. Premont, and R. J. Lefkowitz Heptahelical Receptor Signaling: Beyond the G Protein Paradigm J. Cell Biol., May 31, 1999; 145(5): 927 - 932. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bunemann and M M. Hosey G-protein coupled receptor kinases as modulators of G-protein signalling J. Physiol., May 15, 1999; 517(1): 5 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Roychowdhury, D. Panda, L. Wilson, and M. M. Rasenick G Protein alpha Subunits Activate Tubulin GTPase and Modulate Microtubule Polymerization Dynamics J. Biol. Chem., May 7, 1999; 274(19): 13485 - 13490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Carman, M. P. Lisanti, and J. L. Benovic Regulation of G Protein-coupled Receptor Kinases by Caveolin J. Biol. Chem., March 26, 1999; 274(13): 8858 - 8864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Barak, K. Warabi, X. Feng, M. G. Caron, and M. M. Kwatra Real-time Visualization of the Cellular Redistribution of G Protein-coupled Receptor Kinase 2 and beta -Arrestin 2 during Homologous Desensitization of the Substance P Receptor J. Biol. Chem., March 12, 1999; 274(11): 7565 - 7569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Penela, A. Ruiz-Gomez, J. G. Castano, and F. Mayor Jr. Degradation of the G Protein-coupled Receptor Kinase 2 by the Proteasome Pathway J. Biol. Chem., December 25, 1998; 273(52): 35238 - 35244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. R. Freeman, E. M. D. L. Cruz, T. D. Pollard, R. J. Lefkowitz, and J. A. Pitcher Regulation of G protein-coupled Receptor Kinase 5 (GRK5) by Actin J. Biol. Chem., August 7, 1998; 273(32): 20653 - 20657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Lefkowitz G Protein-coupled Receptors. III. NEW ROLES FOR RECEPTOR KINASES AND beta -ARRESTINS IN RECEPTOR SIGNALING AND DESENSITIZATION J. Biol. Chem., July 24, 1998; 273(30): 18677 - 18680. [Full Text] [PDF]
|
|
|
|
|
|
A. Ruiz-Gomez, J. Humrich, C. Murga, U. Quitterer, M. J. Lohse, and F. Mayor Jr. Phosphorylation of Phosducin and Phosducin-like Protein by G Protein-coupled Receptor Kinase 2 J. Biol. Chem., September 15, 2000; 275(38): 29724 - 29730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Pronin, A. J. Morris, A. Surguchov, and J. L. Benovic Synucleins Are a Novel Class of Substrates for G Protein-coupled Receptor Kinases J. Biol. Chem., August 18, 2000; 275(34): 26515 - 26522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cong, S. J. Perry, F.-T. Lin, I. D. Fraser, L. A. Hu, W. Chen, J. A. Pitcher, J. D. Scott, and R. J. Lefkowitz Regulation of Membrane Targeting of the G Protein-coupled Receptor Kinase 2 by Protein Kinase A and Its Anchoring Protein AKAP79 J. Biol. Chem., April 27, 2001; 276(18): 15192 - 15199. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |