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 Taylor, J. M. Articles by Parsons, J. T. Search for Related Content PubMed PubMed Citation Articles by Taylor, J. M. Articles by Parsons, J. T.

J Biol Chem, Vol. 273, Issue 14, 8063-8070, April 3, 1998

Characterization of Graf, the GTPase-activating Protein for Rho Associated with Focal Adhesion Kinase
PHOSPHORYLATION AND POSSIBLE REGULATION BY MITOGEN-ACTIVATED PROTEIN KINASE

Joan M. Taylor, Jeffrey D. Hildebrand, Christopher P. Mack, Michael E. Cox, and J. Thomas Parsons

From the  Department of Microbiology and  Department of Molecular and Cellular Physiology, Health Sciences Center, University of Virginia, Charlottesville, Virginia 22908

Graf is a GTPase-activating protein for Rho that interacts with focal adhesion kinase and co-localizes with the actin cytoskeleton (Hildebrand, J. D., Taylor, J. M. and Parsons, J. T. (1996) Mol. Cell. Biol. 16, 3169-3178). We examined the expression and regulation of Graf as a prelude to understanding the role of Graf in mediating signal transduction in vivo. We demonstrated that Graf is a ubiquitously expressed 95-kDa protein with high levels observed in heart and brain and cells derived from these tissues. Stimulation of PC12 cells with epidermal growth factor or nerve growth factor induced a phosphatase-reversible mobility shift upon gel electrophoresis, indicative of phosphorylation. In vitro, purified mitogen-activated protein (MAP) kinase catalyzed the phosphorylation of Graf on serine 510, suggesting that Graf phosphorylation may be mediated through MAP kinase signaling. In addition, the mutation of serine 510 to alanine inhibited the epidermal growth factor-induced mobility shift of mutant Graf protein in vivo, consistent with serine 510 being the site of in vivo phosphorylation. Based on these data we suggest that phosphorylation of Graf by MAP kinase or related kinases may be a mechanism by which growth factor signaling modulates Rho-mediated cytoskeletal changes in PC12 and perhaps other cells.

---

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				J. T. Parsons, J. Slack-Davis, R. Tilghman, and W. G. Roberts Focal Adhesion Kinase: Targeting Adhesion Signaling Pathways for Therapeutic Intervention Clin. Cancer Res., February 1, 2008; 14(3): 627 - 632. [Abstract] [Full Text] [PDF]

				J. Shi and J. E. Casanova Invasion of Host Cells by Salmonella typhimurium Requires Focal Adhesion Kinase and p130Cas Mol. Biol. Cell, November 1, 2006; 17(11): 4698 - 4708. [Abstract] [Full Text] [PDF]

				L. H. Romer, K. G. Birukov, and J. G.N. Garcia Focal adhesions: paradigm for a signaling nexus. Circ. Res., March 17, 2006; 98(5): 606 - 616. [Abstract] [Full Text] [PDF]

				A. Pullikuth, E. McKinnon, H.-J. Schaeffer, and A. D. Catling The MEK1 Scaffolding Protein MP1 Regulates Cell Spreading by Integrating PAK1 and Rho Signals Mol. Cell. Biol., June 15, 2005; 25(12): 5119 - 5133. [Abstract] [Full Text] [PDF]

				I. Lavelin and B. Geiger Characterization of a Novel GTPase-activating Protein Associated with Focal Adhesions and the Actin Cytoskeleton J. Biol. Chem., February 25, 2005; 280(8): 7178 - 7185. [Abstract] [Full Text] [PDF]

				X. Wu, S. Suetsugu, L. A. Cooper, T. Takenawa, and J.-L. Guan Focal Adhesion Kinase Regulation of N-WASP Subcellular Localization and Function J. Biol. Chem., March 5, 2004; 279(10): 9565 - 9576. [Abstract] [Full Text] [PDF]

				L. Wang, T. Li, and L. Lu UV-Induced Corneal Epithelial Cell Death by Activation of Potassium Channels Invest. Ophthalmol. Vis. Sci., December 1, 2003; 44(12): 5095 - 5101. [Abstract] [Full Text] [PDF]

				J. T. Parsons Focal adhesion kinase: the first ten years J. Cell Sci., April 15, 2003; 116(8): 1409 - 1416. [Abstract] [Full Text] [PDF]

				E. H.J. Danen, P. Sonneveld, C. Brakebusch, R. Fassler, and A. Sonnenberg The fibronectin-binding integrins {alpha}5{beta}1 and {alpha}v{beta}3 differentially modulate RhoA-GTP loading, organization of cell matrix adhesions, and fibronectin fibrillogenesis J. Cell Biol., December 23, 2002; 159(6): 1071 - 1086. [Abstract] [Full Text] [PDF]

				Y. Liu, J. C. Loijens, K. H. Martin, A. V. Karginov, and J. T. Parsons The Association of ASAP1, an ADP Ribosylation Factor-GTPase Activating Protein, with Focal Adhesion Kinase Contributes to the Process of Focal Adhesion Assembly Mol. Biol. Cell, June 1, 2002; 13(6): 2147 - 2156. [Abstract] [Full Text] [PDF]

				L. Lu, P. S. Reinach, and W. W.-Y. Kao Corneal Epithelial Wound Healing Experimental Biology and Medicine, July 1, 2001; 226(7): 653 - 664. [Abstract] [Full Text] [PDF]

				D. D. Tang and S. J. Gunst Depletion of focal adhesion kinase by antisense depresses contractile activation of smooth muscle Am J Physiol Cell Physiol, April 1, 2001; 280(4): C874 - C883. [Abstract] [Full Text] [PDF]

				J. M. Taylor, C. P. Mack, K. Nolan, C. P. Regan, G. K. Owens, and J. T. Parsons Selective Expression of an Endogenous Inhibitor of FAK Regulates Proliferation and Migration of Vascular Smooth Muscle Cells Mol. Cell. Biol., March 1, 2001; 21(5): 1565 - 1572. [Abstract] [Full Text]

				D. H. Campbell, R. L. Sutherland, and R. J. Daly Signaling Pathways and Structural Domains Required for Phosphorylation of EMS1/Cortactin Cancer Res., October 1, 1999; 59(20): 5376 - 5385. [Abstract] [Full Text] [PDF]

				T. M. Seasholtz, M. Majumdar, and J. H. Brown MINIREVIEW: Rho as a Mediator of G Protein-Coupled Receptor Signaling Mol. Pharmacol., June 1, 1999; 55(6): 949 - 956. [Full Text]

				X.-g. Sun and S. A. Rotenberg Overexpression of Protein Kinase C{{alpha}} in MCF-10A Human Breast Cells Engenders Dramatic Alterations in Morphology, Proliferation, and Motility Cell Growth Differ., May 1, 1999; 10(5): 343 - 352. [Abstract] [Full Text]

				D. I. Johnson Cdc42: An Essential Rho-Type GTPase Controlling Eukaryotic Cell Polarity Microbiol. Mol. Biol. Rev., March 1, 1999; 63(1): 54 - 105. [Abstract] [Full Text] [PDF]

				J. Taylor, M. Macklem, and J. Parsons Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho J. Cell Sci., January 1, 1999; 112(2): 231 - 242. [Abstract] [PDF]

				H.-L. Cheng, M. L. Steinway, J. W. Russell, and E. L. Feldman GTPases and Phosphatidylinositol 3-Kinase Are Critical for Insulin-like Growth Factor-I-mediated Schwann Cell Motility J. Biol. Chem., August 25, 2000; 275(35): 27197 - 27204. [Abstract] [Full Text] [PDF]