| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Center for Craniofacial Biology, Departments of Surgery and Pediatrics, and the Developmental Biology Program, The Childrens Hospital Los Angeles Research Institute, University of Southern California Schools of Dentistry and Medicine, Los Angeles, California 90023; and 2 Equipe Morphogenesis Cellulaire et Tumorale, Institut Curie-Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique, 75248 Paris Cedex 05, France
Murine Sprouty2 (mSpry2) is a conserved ortholog of Drosophila Sprouty, a gene that inhibits several tyrosine kinase receptor pathways, resulting in net reduction of mitogen-activated protein (MAP) kinase activation. However, the precise mechanism mediating mSpry2 function as a negative regulator in tyrosine kinase growth factor pathways that regulate diverse biological functions remains incompletely characterized. Fibroblast growth factor 10 (FGF10) is a key positive regulator of lung branching morphogenesis and induces epithelial expression of mSpry2 adjacent to mesenchymal sites of FGF10. Herein, we demonstrate that FGF10 stimulation of mouse lung epithelial cells (MLE15) overexpressing mSpry2 results in both mSpry2 tyrosine phosphorylation and differential binding of mSpry2 to several key upstream target proteins in the MAP kinase-activating pathway. Thus FGF receptor (FGFR) activation results in increased association of mSpry2 with growth factor receptor-binding protein 2, suc-1-associated nuerotrophic factor target 2, and Raf but decreased binding to protein tyrosine phosphatase 2 and GTPase-activating protein 1, resulting in a net reduction of MAP kinase activation. mSpry2 also spatially translocates to the plasma membrane and intracellular membrane structures in response to FGF10 stimulation. Our data demonstrate novel intracellular mechanisms mediating mSpry2 function as a negative regulator of uncontrolled FGF-induced MAP kinase signaling.
fibroblast growth factor 10 stimulation; murine Sprouty2; differentially binding; mouse lung epithelial cells
This article has been cited by other articles:
|
|
 |
|
  F. Edwin, K. Anderson, C. Ying, and T. B. Patel Intermolecular Interactions of Sprouty Proteins and Their Implications in Development and Disease Mol. Pharmacol., October 1, 2009; 76(4): 679 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Horowitz and M. Simons Branching Morphogenesis Circ. Res., October 10, 2008; 103(8): 784 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Warburton, L. Perin, R. DeFilippo, S. Bellusci, W. Shi, and B. Driscoll Stem/Progenitor Cells in Lung Development, Injury Repair, and Regeneration Proceedings of the ATS, August 15, 2008; 5(6): 703 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Denham, B. J. Conley, F. Olsson, L. Gulluyan, T. J. Cole, and R. Mollard A murine respiratory-inducing niche displays variable efficiency across human and mouse embryonic stem cell species Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1241 - L1247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. V. Cardoso and J. Lu Regulation of early lung morphogenesis: questions, facts and controversies Development, May 1, 2006; 133(9): 1611 - 1624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. White, J. Xu, Y. Yin, C. Smith, G. Schmid, and D. M. Ornitz FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains Development, April 15, 2006; 133(8): 1507 - 1517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Jarvis, S. J. Toering, M. A. Simon, M. A. Krasnow, and R. K. Smith-Bolton Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases Development, March 15, 2006; 133(6): 1133 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. DaSilva, L. Xu, H. J. Kim, W. T. Miller, and D. Bar-Sagi Regulation of sprouty stability by mnk1-dependent phosphorylation. Mol. Cell. Biol., March 1, 2006; 26(5): 1898 - 1907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-i. Ozaki, S. Miyazaki, S. Tanimura, and M. Kohno Efficient suppression of FGF-2-induced ERK activation by the cooperative interaction among mammalian Sprouty isoforms J. Cell Sci., December 15, 2005; 118(24): 5861 - 5871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, V. G. Brunton, H. R. Burgar, L. M. Wheldon, and J. K. Heath FRS2-dependent SRC activation is required for fibroblast growth factor receptor-induced phosphorylation of Sprouty and suppression of ERK activity J. Cell Sci., December 1, 2004; 117(25): 6007 - 6017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Lo, P. Yusoff, C. W. Fong, K. Guo, B. J. McCaw, W. A. Phillips, H. Yang, E. S. M. Wong, H. F. Leong, Q. Zeng, et al. The Ras/Mitogen-Activated Protein Kinase Pathway Inhibitor and Likely Tumor Suppressor Proteins, Sprouty 1 and Sprouty 2 Are Deregulated in Breast Cancer Cancer Res., September 1, 2004; 64(17): 6127 - 6136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chi, S. Zhang, Y. Lin, R. Prunskaite-Hyyrylainen, R. Vuolteenaho, P. Itaranta, and S. Vainio Sprouty proteins regulate ureteric branching by coordinating reciprocal epithelial Wnt11, mesenchymal Gdnf and stromal Fgf7 signalling during kidney development Development, July 15, 2004; 131(14): 3345 - 3356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Upadhyay, M. Bundesmann, V. Panduri, E. Correa-Meyer, and D. W. Kamp Fibroblast Growth Factor-10 Attenuates H2O2-Induced Alveolar Epithelial Cell DNA Damage: Role of MAPK Activation and DNA Repair Am. J. Respir. Cell Mol. Biol., July 1, 2004; 31(1): 107 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Corson, Y. Yamanaka, K.-M. V. Lai, and J. Rossant Spatial and temporal patterns of ERK signaling during mouse embryogenesis Development, October 1, 2003; 130(19): 4527 - 4537. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
