|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 114, Issue 9 1691-1698, Copyright © 2001 by Company of Biologists
JOURNAL ARTICLES |
CS Buensuceso, D Woodside, JL Huff, GE Plopper and TE O'Toole
Department of Vascular Biology, Scripps Research Institute-VB2, La Jolla, CA 92037, USA. totoole@alumni.umich.edu
The scaffolding protein, Rack1, is a seven-WD-domain-containing protein that has been implicated in binding to integrin (&bgr;) subunit cytoplasmic domains and to members of two kinase families (src and protein kinase C, PKC) that mediate integrin bidirectional signaling. To explore the role of Rack1 in integrin function we have transfected this protein in Chinese hamster ovary (CHO) cells. We have observed no effect of Rack1 overexpression on inside-out signaling as the ligand binding properties of CHO cells also expressing constitutively active or inactive integrins were not affected. In contrast, we observed that cells stably or transiently overexpressing Rack1 had decreased migration compared to mock transfected cells. Stable Rack1 transfectants also demonstrated an increased number of actin stress fibers and focal contacts. These effects on motility and cytoskeletal organization did not appear to result from Rack1 inhibition of src function as downstream substrates of this kinase were phosphorylated normally. In addition, expression of an active src construct did not reverse the migratory deficit induced by Rack1 overexpression. On the other hand when we overexpressed a Rack1 variant with alanine substitutions in the putative PKC binding site in its third WD domain, we observed no deficit in migration. Thus the ability of Rack1 to bind, localize and stabilize PKC isoforms is likely to be involved in aspects of integrin outside-in signaling.
This article has been cited by other articles:
|
|
 |
|
  S. Chen, F. Lin, M. E. Shin, F. Wang, L. Shen, and H. E. Hamm RACK1 Regulates Directional Cell Migration by Acting on G{beta}{gamma} at the Interface with Its Effectors PLC{beta} and PI3K{gamma} Mol. Biol. Cell, September 1, 2008; 19(9): 3909 - 3922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Kiely, G. S. Baillie, M. J. Lynch, M. D. Houslay, and R. O'Connor Tyrosine 302 in RACK1 Is Essential for Insulin-like Growth Factor-I-mediated Competitive Binding of PP2A and {beta}1 Integrin and for Tumor Cell Proliferation and Migration J. Biol. Chem., August 22, 2008; 283(34): 22952 - 22961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Valerius, M. Kleinschmidt, N. Rachfall, F. Schulze, S. Lopez Marin, M. Hoppert, K. Streckfuss-Bomeke, C. Fischer, and G. H. Braus The Saccharomyces Homolog of Mammalian RACK1, Cpc2/Asc1p, Is Required for FLO11-dependent Adhesive Growth and Dimorphism Mol. Cell. Proteomics, November 1, 2007; 6(11): 1968 - 1979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kraus, D. Gioeli, T. Vomastek, V. Gordon, and M. J. Weber Receptor for Activated C Kinase 1 (RACK1) and Src Regulate the Tyrosine Phosphorylation and Function of the Androgen Receptor. Cancer Res., November 15, 2006; 66(22): 11047 - 11054. [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]
|
|
|
|
 |
|
 P. A. Kiely, D. O'Gorman, K. Luong, D. Ron, and R. O'Connor Insulin-Like Growth Factor I Controls a Mutually Exclusive Association of RACK1 with Protein Phosphatase 2A and {beta}1 Integrin To Promote Cell Migration. Mol. Cell. Biol., June 1, 2006; 26(11): 4041 - 4051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhang, C. S. Zong, U. Hermanto, P. Lopez-Bergami, Z. Ronai, and L.-H. Wang RACK1 Recruits STAT3 Specifically to Insulin and Insulin-Like Growth Factor 1 Receptors for Activation, Which Is Important for Regulating Anchorage-Independent Growth Mol. Cell. Biol., January 15, 2006; 26(2): 413 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mourtada-Maarabouni, L. Kirkham, F. Farzaneh, and G. T. Williams Functional expression cloning reveals a central role for the receptor for activated protein kinase C 1 (RACK1) in T cell apoptosis J. Leukoc. Biol., August 1, 2005; 78(2): 503 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Kiely, M. Leahy, D. O'Gorman, and R. O'Connor RACK1-mediated Integration of Adhesion and Insulin-like Growth Factor I (IGF-I) Signaling and Cell Migration Are Defective in Cells Expressing an IGF-I Receptor Mutated at Tyrosines 1250 and 1251 J. Biol. Chem., March 4, 2005; 280(9): 7624 - 7633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Buensuceso, A. Obergfell, A. Soriani, K. Eto, W. B. Kiosses, E. G. Arias-Salgado, T. Kawakami, and S. J. Shattil Regulation of Outside-in Signaling in Platelets by Integrin-associated Protein Kinase C{beta} J. Biol. Chem., January 7, 2005; 280(1): 644 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Arya, V. Kedar, J. R. Hwang, H. McDonough, H.-H. Li, J. Taylor, and C. Patterson Muscle ring finger protein-1 inhibits PKC{epsilon} activation and prevents cardiomyocyte hypertrophy J. Cell Biol., December 20, 2004; 167(6): 1147 - 1159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Huang and J. W. Walker Myofilament anchoring of protein kinase C-epsilon in cardiac myocytes J. Cell Sci., April 15, 2004; 117(10): 1971 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Guil, N. de La Iglesia, J. Fernandez-Larrea, D. Cifuentes, J. C. Ferrer, J. J. Guinovart, and M. Bach-Elias Alternative Splicing of the Human Proto-oncogene c-H-ras Renders a New Ras Family Protein That Trafficks to Cytoplasm and Nucleus Cancer Res., September 1, 2003; 63(17): 5178 - 5187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Cox, D. Bennin, A. T. Doan, T. O'Toole, and A. Huttenlocher RACK1 Regulates Integrin-mediated Adhesion, Protrusion, and Chemotactic Cell Migration via Its Src-binding Site Mol. Biol. Cell, February 1, 2003; 14(2): 658 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Dell, J. Connor, S. Chen, E. G. Stebbins, N. P. Skiba, D. Mochly-Rosen, and H. E. Hamm The beta gamma Subunit of Heterotrimeric G Proteins Interacts with RACK1 and Two Other WD Repeat Proteins J. Biol. Chem., December 13, 2002; 277(51): 49888 - 49895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. McCahill, J. Warwicker, G. B. Bolger, M. D. Houslay, and S. J. Yarwood The RACK1 Scaffold Protein: A Dynamic Cog in Cell Response Mechanisms Mol. Pharmacol., December 1, 2002; 62(6): 1261 - 1273. [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Tcherkasowa, S. Adam-Klages, M.-L. Kruse, K. Wiegmann, S. Mathieu, W. Kolanus, M. Kronke, and D. Adam Interaction with Factor Associated with Neutral Sphingomyelinase Activation, a WD Motif-Containing Protein, Identifies Receptor for Activated C-Kinase 1 as a Novel Component of the Signaling Pathways of the p55 TNF Receptor J. Immunol., November 1, 2002; 169(9): 5161 - 5170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Besson, T. L. Wilson, and V. W. Yong The Anchoring Protein RACK1 Links Protein Kinase Cepsilon to Integrin beta Chains. REQUIREMENT FOR ADHESION AND MOTILITY J. Biol. Chem., June 7, 2002; 277(24): 22073 - 22084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Hermanto, C. S. Zong, W. Li, and L.-H. Wang RACK1, an Insulin-Like Growth Factor I (IGF-I) Receptor-Interacting Protein, Modulates IGF-I-Dependent Integrin Signaling and Promotes Cell Spreading and Contact with Extracellular Matrix Mol. Cell. Biol., April 1, 2002; 22(7): 2345 - 2365. [Abstract] [Full Text] [PDF]
|
|
