|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
doi: 10.1242/10.1242/jcs.00105
Research Article |
Department of Cell and Developmental Biology and Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
* Author for correspondence (e-mail: sksastry{at}med.unc.edu)
Accepted 15 August 2002
The cytoplasmic protein tyrosine phosphatase, PTP-PEST, associates with the focal adhesion proteins p130cas and paxillin and has recently been implicated in cell migration. In this study, we investigated the mechanism by which PTP-PEST regulates this phenomenon. We find that PTP-PEST is activated in an adhesion-dependent manner and localizes to the tips of membrane protrusions in spreading fibroblasts. We show that the catalytic activity of PTP-PEST is a key determinant for its effects on motility. Overexpression of PTP-PEST, but not a catalytically inactive form, impairs haptotaxis, cell spreading and formation of membrane protrusions in CHOK1 cells. In addition, overexpression of PTP-PEST in Rat1 fibroblasts perturbs membrane ruffling and motility in response to PDGF stimulation. The expression level of PTP-PEST modulates the activity of the small GTPase, Rac1. PTP-PEST overexpression suppresses activation of Rac1 in response to both integrin-mediated adhesion or growth factor stimulation. In contrast, fibroblasts that lack PTP-PEST expression show enhanced Rac1 activity. Co-expression of constitutively active Rac1 with PTP-PEST overcomes the inhibition of cell spreading and migration indicating that PTP-PEST acts by antagonizing Rac1 activation. Our data suggest a model in which PTP-PEST is activated by integrins and localized to regions where it can control motile events at the leading edge through inhibition of the small GTPase Rac1.
Key words: Cell migration, Rho family GTPases, Tyrosine phosphatase
This article has been cited by other articles:
|
|
 |
|
  N. O. Deakin and C. E. Turner Paxillin comes of age J. Cell Sci., August 1, 2008; 121(15): 2435 - 2444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Lai, W.-C. Lin, and F.-T. Lin PTPL1/FAP-1 Negatively Regulates TRIP6 Function in Lysophosphatidic Acid-induced Cell Migration J. Biol. Chem., August 17, 2007; 282(33): 24381 - 24387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Avraamides, M. E. Bromberg, J. P. Gaughan, S. M. Thomas, A. Y. Tsygankov, and T. S. Panetti Hic-5 promotes endothelial cell migration to lysophosphatidic acid Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H193 - H203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Sahu, S. Nunez, G. Bai, and A. Gupta Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2288 - C2296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Fitsialos, A.-A. Chassot, L. Turchi, M. A. Dayem, K. LeBrigand, C. Moreilhon, G. Meneguzzi, R. Busca, B. Mari, P. Barbry, et al. Transcriptional Signature of Epidermal Keratinocytes Subjected to in Vitro Scratch Wounding Reveals Selective Roles for ERK1/2, p38, and Phosphatidylinositol 3-Kinase Signaling Pathways J. Biol. Chem., May 18, 2007; 282(20): 15090 - 15102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Halle, Y.-C. Liu, S. Hardy, J.-F. Theberge, C. Blanchetot, A. Bourdeau, T.-C. Meng, and M. L. Tremblay Caspase-3 Regulates Catalytic Activity and Scaffolding Functions of the Protein Tyrosine Phosphatase PEST, a Novel Modulator of the Apoptotic Response Mol. Cell. Biol., February 1, 2007; 27(3): 1172 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Rossi, R. Manfredini, F. Bertolini, D. Ferrari, M. Fogli, R. Zini, S. Salati, V. Salvestrini, S. Gulinelli, E. Adinolfi, et al. The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration Blood, January 15, 2007; 109(2): 533 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-J. Lu, W.-Y. Lai, C.-Y. F. Huang, W.-J. Hsieh, J.-S. Yu, Y.-J. Hsieh, W.-T. Chang, T.-H. Leu, W.-C. Chang, W.-J. Chuang, et al. Inhibition of Cell Migration by Autophosphorylated Mammalian Sterile 20-Like Kinase 3 (MST3) Involves Paxillin and Protein-tyrosine Phosphatase-PEST J. Biol. Chem., December 15, 2006; 281(50): 38405 - 38417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Playford, P. D. Lyons, S. K. Sastry, and M. D. Schaller Identification of a Filamin Docking Site on PTP-PEST J. Biol. Chem., November 10, 2006; 281(45): 34104 - 34112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ushio-Fukai Localizing NADPH Oxidase-Derived ROS Sci. Signal., August 22, 2006; 2006(349): re8 - re8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Burridge, S. K. Sastry, and J. L. Sallee Regulation of Cell Adhesion by Protein-tyrosine Phosphatases: I. CELL-MATRIX ADHESION J. Biol. Chem., June 9, 2006; 281(23): 15593 - 15596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Sastry, Z. Rajfur, B. P. Liu, J.-F. Cote, M. L. Tremblay, and K. Burridge PTP-PEST Couples Membrane Protrusion and Tail Retraction via VAV2 and p190RhoGAP J. Biol. Chem., April 28, 2006; 281(17): 11627 - 11636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Wu and L. S. Terada Oxidative Modification of Protein Tyrosine Phosphatases Sci. Signal., April 25, 2006; 2006(332): pl2 - pl2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-C. Ceacareanu, B. Ceacareanu, D. Zhuang, Y. Chang, R. M. Ray, L. Desai, K. E. Chapman, C. M. Waters, and A. Hassid Nitric oxide attenuates IGF-I-induced aortic smooth muscle cell motility by decreasing Rac1 activity: essential role of PTP-PEST and p130cas Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1263 - C1270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Jamieson, D. A. Tumbarello, M. Halle, M. C. Brown, M. L. Tremblay, and C. E. Turner Paxillin is essential for PTP-PEST-dependent regulation of cell spreading and motility: a role for paxillin kinase linker J. Cell Sci., December 15, 2005; 118(24): 5835 - 5847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Wu, Y. C. Xu, Z. Ma, F. E. Nwariaku, G. A. Sarosi Jr., and L. S. Terada Subcellular targeting of oxidants during endothelial cell migration J. Cell Biol., December 5, 2005; 171(5): 893 - 904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Howe, L. C. Baldor, and B. P. Hogan Spatial regulation of the cAMP-dependent protein kinase during chemotactic cell migration PNAS, October 4, 2005; 102(40): 14320 - 14325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zaidel-Bar, Z. Kam, and B. Geiger Polarized downregulation of the paxillin-p130CAS-Rac1 pathway induced by shear flow J. Cell Sci., September 1, 2005; 118(17): 3997 - 4007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Barwe, G. Anilkumar, S. Y. Moon, Y. Zheng, J. P. Whitelegge, S. A. Rajasekaran, and A. K. Rajasekaran Novel Role for Na,K-ATPase in Phosphatidylinositol 3-Kinase Signaling and Suppression of Cell Motility Mol. Biol. Cell, March 1, 2005; 16(3): 1082 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Srivastava, B. E. Elliott, D. Louvard, and M. Arpin Src-dependent Ezrin Phosphorylation in Adhesion-mediated Signaling Mol. Biol. Cell, March 1, 2005; 16(3): 1481 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Carton, D. Hermans, and J. Eggermont Hypotonicity induces membrane protrusions and actin remodeling via activation of small GTPases Rac and Cdc42 in Rat-1 fibroblasts Am J Physiol Cell Physiol, October 1, 2003; 285(4): C935 - C944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Koivisto, K. Alavian, L. Hakkinen, S. Pelech, C. A. McCulloch, and H. Larjava Glycogen synthase kinase-3 regulates formation of long lamellipodia in human keratinocytes J. Cell Sci., September 15, 2003; 116(18): 3749 - 3760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Laakko and R. L. Juliano Adhesion Regulation of Stromal Cell-derived Factor-1 Activation of ERK in Lymphocytes by Phosphatases J. Biol. Chem., August 22, 2003; 278(34): 31621 - 31628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Goldfinger, J. Han, W. B. Kiosses, A. K. Howe, and M. H. Ginsberg Spatial restriction of {alpha}4 integrin phosphorylation regulates lamellipodial stability and {alpha}4{beta}1-dependent cell migration J. Cell Biol., August 18, 2003; 162(4): 731 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. DeMali and K. Burridge Coupling membrane protrusion and cell adhesion J. Cell Sci., June 15, 2003; 116(12): 2389 - 2397. [Abstract] [Full Text] [PDF]
|
|
