| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Laboratory of Molecular Pathogenesis, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan [A. R. M. R. A., M. L. O., T. S., N. S., M. H.], and The Burnham Institute, La Jolla, California 92037 [G-S. F.]
We investigated the role of SH2 domain containing protein tyrosine phosphatase (SHP) 2 in Concanavalin A (Con A) -dependent signaling that leads to the augmented secretion and activation of matrix metalloproteinase (MMP) 2. In cells expressing mutant SHP-2 in which 65 amino acids in the SH2-N domain were deleted, we found that production, secretion, and proteolytic activation of MMP-2 in response to Con A treatment was severely impaired. Under Con A stimulation, complex formation of SHP-2 with SOS-1 and Grb-2 together with the activation of Ras signaling was clearly observed in wild-type cells, but not in SHP-2 mutant cells. In wild-type cells, Con A-treatment activated dual signaling pathways, extracellular signal-regulated kinase (Erk) and p38, in a Ras-dependent manner, whereas Con A-dependent activation of these signaling pathways was absent in SHP-2 mutant cells. In addition, pretreatment of wild-type cells with U0126, a potent inhibitor for mitogen-activated protein/ERK kinase 1, or with SB203580, a specific inhibitor for p38, significantly inhibited the Con A-dependent secretion and activation of MMP-2. However, overexpression of active mitogen-activated protein/ERK kinase 1 in SHP-2 mutant cells could not induce clear activation of MMP-2 secretion, although these cells responded well to the Con A treatment in a p38-dependent manner. Finally, reintroduction of wild-type SHP-2 into SHP-2 mutant cells rescued Erk and p38 activation, and also MMP-2 secretion, whereas dominant-negative SHP-2 could block the Con A-dependent activation of Erk and p38. Taken together, our results strongly suggest that SHP-2 plays a critical role as a positive mediator for Con A-dependent activation of MMP-2 secretion via Ras-Erk and Ras-p38 signalings.
This article has been cited by other articles:
|
|
 |
|
  Z. Zhang, B. D. Humphreys, and J. V. Bonventre Shedding of the Urinary Biomarker Kidney Injury Molecule-1 (KIM-1) Is Regulated by MAP Kinases and Juxtamembrane Region J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2704 - 2714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.R.M. Ruhul Amin, M. H. Uddin Biswas, T. Senga, G.-S. Feng, R. Kannagi, M. L. Agarwal, and M. Hamaguchi A role for SHPS-1/SIRP{alpha} in Concanavalin A-dependent production of MMP-9 Genes Cells, September 1, 2007; 12(9): 1023 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.R.M. R. Amin, R. K. Paul, V. S. Thakur, and M. L. Agarwal A Novel Role for p73 in the Regulation of Akt-Foxo1a-Bim Signaling and Apoptosis Induced by the Plant Lectin, Concanavalin A Cancer Res., June 15, 2007; 67(12): 5617 - 5621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ben-David, B. V. Aruna, R. Seger, M. Sela, and E. Mozes A 50-kDa ERK-like protein is up-regulated by a dual altered peptide ligand that suppresses myasthenia gravis-associated responses PNAS, November 28, 2006; 103(48): 18232 - 18237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Krenz, K. E. Yutzey, and J. Robbins Noonan Syndrome Mutation Q79R in Shp2 Increases Proliferation of Valve Primordia Mesenchymal Cells via Extracellular Signal-Regulated Kinase 1/2 Signaling Circ. Res., October 14, 2005; 97(8): 813 - 820. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
