| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print October 23, 2003
Friedrich Miescher Institute, Basel, BS CH-4058
Corresponding Author: nagamine{at}fmi.ch
We have shown previously that cytoskeletal reorganization (CSR) induced by pharmacological reagents such as colchicine or cytochalasins can upregulate the urokinase-type plasminogen activator (uPA) gene via the Ras/Erk signaling pathway. In this present study using the siRNA technique, we have found that ShcA adapter proteins play a rather active role in CSR-induced Erk activation, contrary to their mostly redundant role in other signaling pathways, e.g. growth factor-induced Erk activation, where Grb2 can bind directly to the receptor tyrosine kinase and activate Erk in the absence of ShcA. ShcA knockdown abolished CSR-induced activation of both Erk and the uPA promoter. Expression of siRNA-escaping silent mutants of p52 or p46 but not p66 ShcA isoform efficiently rescued CSR-induced Erk activation. Moreover, we have shown that phosphorylation of either Y239/240 or Y313 in p52ShcA can mediate CSR-induced Erk activation equally well. In a quest for molecules upstream of ShcA in this signaling, we found that CSR-induced ShcA tyrosine phosphorylation, its association with Grb2, Erk activation and uPA gene expression were all dependent on Rho kinase, p38 MAP kinase and Src. In summary, we have found a novel, non-redundant role for ShcA, in contrast to its redundant role in many other signaling pathways.
J. Biol. Chem, 10.1074/jbc.M310010200
Submitted on September 9, 2003
Revised on October 13, 2003
Accepted on October 23, 2003
Non-redundant role of ShcA in Erk activation by cytoskeletal reorganization
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Arany, A. Faisal, Y. Nagamine, and R. L. Safirstein p66shc Inhibits Pro-survival Epidermal Growth Factor Receptor/ERK Signaling during Severe Oxidative Stress in Mouse Renal Proximal Tubule Cells J. Biol. Chem., March 7, 2008; 283(10): 6110 - 6117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Honma, O. Higuchi, M. Shirakata, T. Yasuda, H. Shibuya, S.-i. Iemura, T. Natsume, and Y. Yamanashi Dok-3 sequesters Grb2 and inhibits the Ras-Erk pathway downstream of protein-tyrosine kinases Genes Cells, February 1, 2006; 11(2): 143 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Qian, K. J. Liu, Y. Chen, D. C. Flynn, V. Castranova, and X. Shi Cdc42 Regulates Arsenic-induced NADPH Oxidase Activation and Cell Migration through Actin Filament Reorganization J. Biol. Chem., February 4, 2005; 280(5): 3875 - 3884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Venugopal, K. Hanashiro, Z.-Z. Yang, and Y. Nagamine Identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes PNAS, December 7, 2004; 101(49): 17120 - 17125. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
