| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 29, 18268-18272, July 17, 1998
From the Departments of ¶ Medicine,
Urokinase-type plasminogen
activator (uPA) binds to cells via a specific
glycosylphosphatidylinositol-anchored receptor. Although occupancy of
the uPA receptor (uPAR) has been shown to alter cellular function and
to induce gene expression, the signaling mechanism has not been
characterized. Urokinase induced an increase in the tyrosine
phosphorylation of multiple proteins in bovine aortic endothelial
cells. In contrast, low molecular weight uPA did not induce this
response. Analysis by immunoblotting demonstrated tyrosine
phosphorylation of focal adhesion kinase (FAK), the focal adhesion-associated proteins paxillin and p130cas,
and mitogen-activated protein kinase (MAPK) following the
occupancy of the uPAR by uPA. Treatment of cells with
phosphatidylinositol-specific phospholipase C, which cleaves
glycosylphosphatidylinositol-linked proteins from the cell surface,
blocked the uPA-induced tyrosine phosphorylation of FAK, indicating the
requirement of an intact uPAR on the cell surface. The uPA-induced
activation of MAPK was completely inhibited by genistein, but not by
4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, a specific inhibitor of Src family kinases. Thus, this study
demonstrates a novel role for the uPAR in endothelial cell signal
transduction that involves the activation of FAK and MAPK, which are
mediated by the receptor-binding domain of uPA. This may have important implications for the mechanism through which uPA influences cell migration and differentiation.
The Urokinase-type Plasminogen Activator Receptor Mediates
Tyrosine Phosphorylation of Focal Adhesion Proteins and Activation of
Mitogen-activated Protein Kinase in Cultured Endothelial Cells
,, and
Pharmacology, and Biochemistry,
Vanderbilt University School of Medicine and Nashville Veterans Affairs
Medical Center, Nashville, Tennessee 37232
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:
|
|
 |
|
  Y. Liu, D. J. Cao, I. M. Sainz, Y.-L. Guo, and R. W. Colman The inhibitory effect of HKa in endothelial cell tube formation is mediated by disrupting the uPA-uPAR complex and inhibiting its signaling and internalization Am J Physiol Cell Physiol, July 1, 2008; 295(1): C257 - C267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shetty, G. N. Rao, D. B. Cines, and K. Bdeir Urokinase induces activation of STAT3 in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L772 - L780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Alfano, I. Iaccarino, and M. P. Stoppelli Urokinase Signaling through Its Receptor Protects against Anoikis by Increasing BCL-xL Expression Levels J. Biol. Chem., June 30, 2006; 281(26): 17758 - 17767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Menshikov, O. Plekhanova, H. Cai, K. Chalupsky, Y. Parfyonova, P. Bashtrikov, V. Tkachuk, and B. C. Berk Urokinase Plasminogen Activator Stimulates Vascular Smooth Muscle Cell Proliferation Via Redox-Dependent Pathways Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 801 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Lakka, C. S. Gondi, D. H. Dinh, W. C. Olivero, M. Gujrati, V. H. Rao, C. Sioka, and J. S. Rao Specific Interference of Urokinase-type Plasminogen Activator Receptor and Matrix Metalloproteinase-9 Gene Expression Induced by Double-stranded RNA Results in Decreased Invasion, Tumor Growth, and Angiogenesis in Gliomas J. Biol. Chem., June 10, 2005; 280(23): 21882 - 21892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jo, K. S. Thomas, N. Marozkina, T. J. Amin, C. M. Silva, S. J. Parsons, and S. L. Gonias Dynamic Assembly of the Urokinase-type Plasminogen Activator Signaling Receptor Complex Determines the Mitogenic Activity of Urokinase-type Plasminogen Activator J. Biol. Chem., April 29, 2005; 280(17): 17449 - 17457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Maupas-Schwalm, C. Robinet, N. Auge, J.-C. Thiers, V. Garcia, J.-P. Cambus, R. Salvayre, and A. Negre-Salvayre Activation of the {beta}-Catenin/T-Cell-Specific Transcription Factor/Lymphoid Enhancer Factor-1 Pathway by Plasminogen Activators in ECV304 Carcinoma Cells Cancer Res., January 15, 2005; 65(2): 526 - 532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Bernstein, R. S. Greenberg, L. Taliana, and S. K. Masur Urokinase Anchors uPAR to the Actin Cytoskeleton Invest. Ophthalmol. Vis. Sci., September 1, 2004; 45(9): 2967 - 2977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Xu, R. D. Balsara, N. V. Gorlatova, D. A. Lawrence, F. J. Castellino, and V. A. Ploplis Conservation of Critical Functional Domains in Murine Plasminogen Activator Inhibitor-1 J. Biol. Chem., April 23, 2004; 279(17): 17914 - 17920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Scortegagna, M. A. Morris, Y. Oktay, M. Bennett, and J. A. Garcia The HIF family member EPAS1/HIF-2{alpha} is required for normal hematopoiesis in mice Blood, September 1, 2003; 102(5): 1634 - 1640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shetty, K. Bdeir, D. B. Cines, and S. Idell Induction of Plasminogen Activator Inhibitor-1 by Urokinase in Lung Epithelial Cells J. Biol. Chem., May 9, 2003; 278(20): 18124 - 18131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jo, K. S. Thomas, D. M. O'Donnell, and S. L. Gonias Epidermal Growth Factor Receptor-dependent and -independent Cell-signaling Pathways Originating from the Urokinase Receptor J. Biol. Chem., January 10, 2003; 278(3): 1642 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shetty, U. R. Pendurthi, P. K. S. Halady, A. O. Azghani, and S. Idell Urokinase induces its own expression in Beas2B lung epithelial cells Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L319 - L328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Smith, O. Boutaud, M. Breyer, J. D. Morrow, J. A. Oates, and D. E. Vaughan Cyclooxygenase-2-Dependent Prostacyclin Formation Is Regulated by Low Density Lipoprotein Cholesterol In Vitro Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 983 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Heiss, E. H. Simon, B. C.M. Beyer, K. U. Gruetzner, A. Tarabichi, R. Babic, F. W. Schildberg, and H. Allgayer Minimal Residual Disease in Gastric Cancer: Evidence of an Independent Prognostic Relevance of Urokinase Receptor Expression by Disseminated Tumor Cells in the Bone Marrow J. Clin. Oncol., April 15, 2002; 20(8): 2005 - 2016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jo, K. S. Thomas, A. V. Somlyo, A. P. Somlyo, and S. L. Gonias Cooperativity between the Ras-ERK and Rho-Rho Kinase Pathways in Urokinase-type Plasminogen Activator-stimulated Cell Migration J. Biol. Chem., March 29, 2002; 277(14): 12479 - 12485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Zamir and B. Geiger Molecular complexity and dynamics of cell-matrix adhesions J. Cell Sci., March 12, 2002; 114(20): 3583 - 3590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ma, D. J. Webb, M. Jo, and S. L. Gonias Endogenously produced urokinase-type plasminogen activator is a major determinant of the basal level of activated ERK/MAP kinase and prevents apoptosis in MDA-MB-231 breast cancer cells J. Cell Sci., March 11, 2002; 114(18): 3387 - 3396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Krishnamoorthy, B. Darnay, B. Aggarwal, D. H. Dinh, G. Kouraklis, W. C. Olivero, M. Gujrati, and J. S. Rao Glioma Cells Deficient in Urokinase Plaminogen Activator Receptor Expression Are Susceptible to Tumor Necrosis Factor-{alpha}-related Apoptosis-inducing Ligand-induced Apoptosis Clin. Cancer Res., December 1, 2001; 7(12): 4195 - 4201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Webb, K. S. Thomas, and S. L. Gonias Plasminogen Activator Inhibitor 1 Functions as a Urokinase Response Modifier at the Level of Cell Signaling and Thereby Promotes MCF-7 Cell Growth J. Cell Biol., February 20, 2001; 152(4): 741 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Li, A. Duzgun, B. E. Sumpio, and M. D. Basson Integrin and FAK-mediated MAPK activation is required for cyclic strain mitogenic effects in Caco-2 cells Am J Physiol Gastrointest Liver Physiol, January 1, 2001; 280(1): G75 - G87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Kroon, P. Koolwijk, B. van der Vecht, and V. W. M. van Hinsbergh Urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia: implications for capillary-like tube formation in a fibrin matrix Blood, October 15, 2000; 96(8): 2775 - 2783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Sitrin, P. M. Pan, H. A. Harper, R. F. Todd III, D. M. Harsh, and R. A. Blackwood Clustering of Urokinase Receptors (uPAR; CD87) Induces Proinflammatory Signaling in Human Polymorphonuclear Neutrophils J. Immunol., September 15, 2000; 165(6): 3341 - 3349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A J Wilson and P R Gibson Role of urokinase and its receptor in basal and stimulated colonic epithelial cell migration in vitro Gut, July 1, 2000; 47(1): 105 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. GUO, A. A.-R. HIGAZI, A. ARAKELIAN, B. S. SACHAIS, D. CINES, R. H. GOLDFARB, T. R. JONES, H. KWAAN, A. P. MAZAR, and S. A. RABBANI A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo FASEB J, July 1, 2000; 14(10): 1400 - 1410. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Farias-Eisner, L. Vician, A. Silver, S. Reddy, S. A. Rabbani, and H. R. Herschman The Urokinase Plasminogen Activator Receptor (UPAR) Is Preferentially Induced by Nerve Growth Factor in PC12 Pheochromocytoma Cells and Is Required for NGF-Driven Differentiation J. Neurosci., January 1, 2000; 20(1): 230 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Webb, D. Nguyen, and S. Gonias Extracellular signal-regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and matrigel invasion J. Cell Sci., January 1, 2000; 113(1): 123 - 134. [Abstract] [PDF]
|
|
|
|
|
|
R. G. Sitrin, P. M. Pan, H. A. Harper, R. A. Blackwood, and R. F. Todd III Urokinase Receptor (CD87) Aggregation Triggers Phosphoinositide Hydrolysis and Intracellular Calcium Mobilization in Mononuclear Phagocytes J. Immunol., December 1, 1999; 163(11): 6193 - 6200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Aguirre Ghiso, K. Kovalski, and L. Ossowski Tumor Dormancy Induced by Downregulation of Urokinase Receptor in Human Carcinoma Involves Integrin and MAPK Signaling J. Cell Biol., October 4, 1999; 147(1): 89 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Carriero, S. D. Vecchio, M. Capozzoli, P. Franco, L. Fontana, A. Zannetti, G. Botti, G. D'Aiuto, M. Salvatore, and M. P. Stoppelli Urokinase Receptor Interacts with {{alpha}}v{{beta}}5 Vitronectin Receptor, Promoting Urokinase-dependent Cell Migration in Breast Cancer Cancer Res., October 1, 1999; 59(20): 5307 - 5314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, L. Hernandez-Lagunas, W. C. Horne, and R. Baron Cytoskeleton-dependent Tyrosine Phosphorylation of the p130Cas Family Member HEF1 Downstream of the G Protein-coupled Calcitonin Receptor. CALCITONIN INDUCES THE ASSOCIATION OF HEF1, PAXILLIN, AND FOCAL ADHESION KINASE J. Biol. Chem., August 27, 1999; 274(35): 25093 - 25098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Dumler, A. Kopmann, K. Wagner, O. A. Mayboroda, U. Jerke, R. Dietz, H. Haller, and D. C. Gulba Urokinase Induces Activation and Formation of Stat4 and Stat1-Stat2 Complexes in Human Vascular Smooth Muscle Cells J. Biol. Chem., August 20, 1999; 274(34): 24059 - 24065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Bhat, J. J. Gunaje, and S. Idell Urokinase-type plasminogen activator induces tyrosine phosphorylation of a 78-kDa protein in H-157 cells Am J Physiol Lung Cell Mol Physiol, August 1, 1999; 277(2): L301 - L309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H.D. Nguyen, A. D. Catling, D. J. Webb, M. Sankovic, L. A. Walker, A. V. Somlyo, M. J. Weber, and S. L. Gonias Myosin Light Chain Kinase Functions Downstream of Ras/ERK to Promote Migration of Urokinase-type Plasminogen Activator-stimulated Cells in an Integrin-selective Manner J. Cell Biol., July 12, 1999; 146(1): 149 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Kroon, P. Koolwijk, H. van Goor, U. H. Weidle, A. Collen, G. van der Pluijm, and V. W. M. van Hinsbergh Role and Localization of Urokinase Receptor in the Formation of New Microvascular Structures in Fibrin Matrices Am. J. Pathol., June 1, 1999; 154(6): 1731 - 1742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Zhang, R. Sakthivel, D. Kniss, C. H. Graham, D. K. Strickland, and K. R. McCrae The Low Density Lipoprotein Receptor-related Protein/alpha 2-Macroglobulin Receptor Regulates Cell Surface Plasminogen Activator Activity on Human Trophoblast Cells J. Biol. Chem., November 27, 1998; 273(48): 32273 - 32280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ghosh, R. Brown, J. C. R. Jones, S. M. Ellerbroek, and M. S. Stack Urinary-type Plasminogen Activator (uPA) Expression and uPA Receptor Localization Are Regulated by alpha 3beta 1 Integrin in Oral Keratinocytes J. Biol. Chem., July 28, 2000; 275(31): 23869 - 23876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tarui, A. P. Mazar, D. B. Cines, and Y. Takada Urokinase-type Plasminogen Activator Receptor (CD87) Is a Ligand for Integrins and Mediates Cell-Cell Interaction J. Biol. Chem., February 2, 2001; 276(6): 3983 - 3990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mukhina, V. Stepanova, D. Traktouev, A. Poliakov, R. Beabealashvilly, Y. Gursky, M. Minashkin, A. Shevelev, and V. Tkachuk The Chemotactic Action of Urokinase on Smooth Muscle Cells Is Dependent on Its Kringle Domain. CHARACTERIZATION OF INTERACTIONS AND CONTRIBUTION TO CHEMOTAXIS J. Biol. Chem., May 26, 2000; 275(22): 16450 - 16458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. D. Nguyen, D. J. Webb, A. D. Catling, Q. Song, A. Dhakephalkar, M. J. Weber, K. S. Ravichandran, and S. L. Gonias Urokinase-type Plasminogen Activator Stimulates the Ras/Extracellular Signal-regulated Kinase (ERK) Signaling Pathway and MCF-7 Cell Migration by a Mechanism That Requires Focal Adhesion Kinase, Src, and Shc. RAPID DISSOCIATION OF GRB2/SOS-SHC COMPLEX IS ASSOCIATED WITH THE TRANSIENT PHOSPHORYLATION OF ERK IN UROKINASE-TREATED CELLS J. Biol. Chem., June 16, 2000; 275(25): 19382 - 19388. [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 |
