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

J. Biol. Chem., Vol. 279, Issue 35, 36593-36600, August 27, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/35/36593    most recent M402084200v1 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 Kang, S. K. Articles by Im, M.-J. Search for Related Content PubMed PubMed Citation Articles by Kang, S. K. Articles by Im, M.-J. Social Bookmarking                      What's this?

_1B-Adrenoceptor Signaling and Cell Motility

GTPase FUNCTION OF G_h/TRANSGLUTAMINASE 2 INHIBITS CELL MIGRATION THROUGH INTERACTION WITH CYTOPLASMIC TAIL OF INTEGRIN SUBUNITS^*

Sung Koo Kang, Kye Sook Yi, Nyoun Soo Kwon¶, Kwang-Hyun Park, Uh-Hyun Kim, Kwang Jin Baek¶, and Mie-Jae Im||

From the Oriental Herbal Research Institute, Dongkuk University, ^¶Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul 156-756, and Department of Biochemistry, Medical School, Chonbuk National University, Keumam-dong, Jeonju 561-182, Republic of Korea

A multifunctional enzyme, G_h, is a GTP-binding protein that couples to the _1B-adrenoreceptor and stimulates phospholipase C-1 but also displays transglutaminase 2 (TG2) activity. G_h/TG2 has been implicated to play a role in cell motility. In this study we have examined which function of G_h/TG2 is involved in this cellular response and the molecular basis. Treatment of human aortic smooth muscle cell with epinephrine inhibits migration to fibronectin and vitronectin, and the inhibition is blocked by the ₁-adrenoreceptor antagonist prazosin or chloroethylclonidine. Up-regulation or overexpression of G_h/TG2 in human aortic smooth muscle cells, DDT1-MF2, or human embryonic kidney cells, HEK 293 cells, results in inhibition of the migratory activity, and stimulation of the _1B-adrenoreceptor with the ₁ agonist further augments the inhibition of migration of human aortic smooth muscle cells and DDT1-MF2. G_h/TG2 is coimmunoprecipitated by an integrin ₅ antibody and binds to the cytoplasmic tail peptide of integrins ₅, _v, and _IIb subunits in the presence of guanosine 5'-3-O-(thio)triphosphate (GTPS). Mutation of Lys-Arg residues in the GFFKR motif, present in the ₅-tail, significantly reduces the binding of GTPS-G_h/TG2. Moreover, the motif-containing integrin ₅-tail peptides block G_h/TG2 coimmunoprecipitation and reverse the inhibition of the migratory activity of HEK 293 cells caused by overexpression G_h/TG2. These results provide evidence that G_h function initiates the modulation of cell motility via association of GTP-bound G_h/TG2 with the GFFKR motif located in integrin subunits.

Received for publication, February 25, 2004 , and in revised form, May 24, 2004.

^* This work was supported by Korea Research Foundation Grant KRF-2003-015-E00065 (to K. J. B.) and Chonbuk National Univerisity Research Fund, 1999 (to U.-H. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Dept. of Biochemistry, Medical School, Chonbuk National University, Keumam-dong, Jeonju 561-182, Republic of Korea. Fax: 82-63-274-9833; E-mail: imm{at}chonbuk.ac.kr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. A. Johnson, D. M. Rose, and R. A. Terkeltaub Factor XIIIA mobilizes transglutaminase 2 to induce chondrocyte hypertrophic differentiation J. Cell Sci., July 1, 2008; 121(13): 2256 - 2264. [Abstract] [Full Text] [PDF]

				K. A. Johnson, M. Polewski, and R. A. Terkeltaub Transglutaminase 2 Is Central to Induction of the Arterial Calcification Program by Smooth Muscle Cells Circ. Res., March 14, 2008; 102(5): 529 - 537. [Abstract] [Full Text] [PDF]

				W. T. Gerthoffer Mechanisms of Vascular Smooth Muscle Cell Migration Circ. Res., March 16, 2007; 100(5): 607 - 621. [Abstract] [Full Text] [PDF]

				Y.-F. Lin, M.-J. Tseng, H.-L. Hsu, Y.-W. Wu, Y.-H. Lee, and Y.-H. Tsai A Novel Follicle-Stimulating Hormone-Induced G{alpha}h/Phospholipase C-{delta}1 Signaling Pathway Mediating Rat Sertoli Cell Ca2+-Influx Mol. Endocrinol., October 1, 2006; 20(10): 2514 - 2527. [Abstract] [Full Text] [PDF]

				Z. Balajthy, K. Csomos, G. Vamosi, A. Szanto, M. Lanotte, and L. Fesus Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions Blood, September 15, 2006; 108(6): 2045 - 2054. [Abstract] [Full Text] [PDF]

				T. Shi, Z.-H. Duan, R. Papay, E. Pluskota, R. J. Gaivin, C. A. de la Motte, E. F. Plow, and D. M. Perez Novel {alpha}1-Adrenergic Receptor Signaling Pathways: Secreted Factors and Interactions with the Extracellular Matrix Mol. Pharmacol., July 1, 2006; 70(1): 129 - 142. [Abstract] [Full Text] [PDF]

				K. A. Johnson and R. A. Terkeltaub External GTP-bound Transglutaminase 2 Is a Molecular Switch for Chondrocyte Hypertrophic Differentiation and Calcification J. Biol. Chem., April 15, 2005; 280(15): 15004 - 15012. [Abstract] [Full Text] [PDF]

				K. Y. Chae, J.-H. Kim, W.-J. Park, Y.-G. Kim, H.-Y. Yun, N. S. Kwon, M.-J. Im, and K. J. Baek Distinct pH Modulation for Dual Function of G{alpha}h (Transglutaminase II) J. Biochem., March 1, 2005; 137(3): 407 - 413. [Abstract] [Full Text] [PDF]