|
Originally published In Press as doi:10.1074/jbc.M008847200 on April 23, 2001
J. Biol. Chem., Vol. 276, Issue 26, 23341-23348, June 29, 2001
Membrane Proximal ERK Signaling Is Required for M-calpain
Activation Downstream of Epidermal Growth Factor Receptor
Signaling*
Angela
Glading ,
Florian
Überall§,
Stephen M.
Keyse¶,
Douglas A.
Lauffenburger , and
Alan
Wells **
From the Department of Pathology, University of
Pittsburgh, Pittsburgh, Pennsylvania 15261, the § Institute
of Medical Chemistry and Biochemistry, University of Innsbruck, A-6020
Innsbruck, Austria, the ¶ Imperial Cancer Research Fund Molecular
Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital,
Dundee, DD1 9SY, United Kingdom, and the Division of
Bioengineering and Environmental Health, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139
Localization of signaling is critical
in directing cellular outcomes, especially in pleiotropic signaling
pathways. The extracellular signal-regulated kinase
(ERK)/microtubule-associated protein kinase, which promotes cell
migration, proliferation, and differentiation is found in the nucleus
and throughout the cytoplasm. Recently, it has been shown that nuclear
translocation of ERK is required for transcriptional changes and cell
proliferation. However, the cellular consequences, of
cytoplasmic signaling have not been defined. We explored whether
cytoplasmic, specifically membrane-proximal, ERK signaling is involved
in growth factor-induced cell motility. We previously have demonstrated
that increased M-calpain activity downstream of epidermal growth factor
receptor (EGFR)-mediated ERK activation is necessary for epidermal
growth factor (EGF)-induced motility. Calpain isoforms also have been
found in nuclear, cytosolic, and plasma membrane-associated
compartments in a variety of cell types. We now employ cell engineering
approaches to control localization of the upstream EGFR and ERK
activities to examine the spatial effect of upstream signal locale on
downstream calpain activity. With differential ligand-induced
internalization and trafficking-restricted receptor variants, we find
that calpain activity is triggered only by plasma membrane-restricted
activated EGFR, not by internalized (although still active) EGFR. Cells
transfected with membrane-targeted ERK1 and ERK2, which sequester
endogenous ERKs, exhibited normal EGF-induced calpain activity.
Transfection of an inactive ERK phosphatase (MKP-3/Pyst1) that
sequesters ERK in the cytoplasm prevented calpain activation as well as
de-adhesion. These data strongly suggest that EGF-induced calpain
activity can be enhanced near sites of membrane-proximal EGFR-mediated
ERK signaling, providing insights about how calpain activity might be
regulated and targeted to enhance its effects on adhesion-related substrates.
*
This study was supported by NIGMS, National Institutes of
Health (NIH), Grant GM54739, a grant from the Department of
Defense/Veterans Affairs Initiative on Combat Casualty (to A. W.), and
NCI, NIH, Grant CA69213 (to D. A. L.), and the Austrian Fond SFB,
F208.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
**
To whom correspondence should be addressed: Dept. of Pathology, 713 Scaife Hall, University of Pittsburgh, Pittsburgh, PA 15261. Tel.:
412-647-7813; Fax: 412-647-8567; E-mail: wellsa@msx.upmc.edu.
Copyright © 2001 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:

|
 |

|
 |
 
B. Casar, I. Arozarena, V. Sanz-Moreno, A. Pinto, L. Agudo-Ibanez, R. Marais, R. E. Lewis, M. T. Berciano, and P. Crespo
Ras Subcellular Localization Defines Extracellular Signal-Regulated Kinase 1 and 2 Substrate Specificity through Distinct Utilization of Scaffold Proteins
Mol. Cell. Biol.,
March 1, 2009;
29(5):
1338 - 1353.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Wang, V. Patel, H. Miyazaki, J.S. Gutkind, and W.A. Yeudall
Role for EPS8 in squamous carcinogenesis
Carcinogenesis,
January 1, 2009;
30(1):
165 - 174.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. D. Smith, Z. M. Jaffer, J. Chernoff, and A. J. Ridley
PAK1-mediated activation of ERK1/2 regulates lamellipodial dynamics
J. Cell Sci.,
November 15, 2008;
121(22):
3729 - 3736.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Sprague, T. S. Fraley, H. S. Jang, S. Lal, and J. A. Greenwood
Phosphoinositide Binding to the Substrate Regulates Susceptibility to Proteolysis by Calpain
J. Biol. Chem.,
April 4, 2008;
283(14):
9217 - 9223.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Badowski, G. Pawlak, A. Grichine, A. Chabadel, C. Oddou, P. Jurdic, M. Pfaff, C. Albiges-Rizo, and M. R. Block
Paxillin Phosphorylation Controls Invadopodia/Podosomes Spatiotemporal Organization
Mol. Biol. Cell,
February 1, 2008;
19(2):
633 - 645.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. J. Joslin, L. K. Opresko, A. Wells, H. S. Wiley, and D. A. Lauffenburger
EGF-receptor-mediated mammary epithelial cell migration is driven by sustained ERK signaling from autocrine stimulation
J. Cell Sci.,
October 15, 2007;
120(20):
3688 - 3699.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Miyazaki, K. Honda, and H. Ohata
Requirement of Ca2+ influx- and phosphatidylinositol 3-kinase-mediated m-calpain activity for shear stress-induced endothelial cell polarity
Am J Physiol Cell Physiol,
October 1, 2007;
293(4):
C1216 - C1225.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Nuzzi, M. A. Senetar, and A. Huttenlocher
Asymmetric Localization of Calpain 2 during Neutrophil Chemotaxis
Mol. Biol. Cell,
March 1, 2007;
18(3):
795 - 805.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Xu and X. Deng
Suppression of Cancer Cell Migration and Invasion by Protein Phosphatase 2A through Dephosphorylation of {micro}- and m-Calpains
J. Biol. Chem.,
November 17, 2006;
281(46):
35567 - 35575.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Shao, J. Chou, C. J. Baty, N. A. Burke, S. C. Watkins, D. B. Stolz, and A. Wells
Spatial Localization of m-Calpain to the Plasma Membrane by Phosphoinositide Biphosphate Binding during Epidermal Growth Factor Receptor-Mediated Activation.
Mol. Cell. Biol.,
July 1, 2006;
26(14):
5481 - 5496.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Tomas, B. Yermen, L. Min, J. E. Pessin, and P. A. Halban
Regulation of pancreatic {beta}-cell insulin secretion by actin cytoskeleton remodelling: role of gelsolin and cooperation with the MAPK signalling pathway
J. Cell Sci.,
May 15, 2006;
119(10):
2156 - 2167.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L.-T. Su, M. A. Agapito, M. Li, W. T. N. Simonson, A. Huttenlocher, R. Habas, L. Yue, and L. W. Runnels
TRPM7 Regulates Cell Adhesion by Controlling the Calcium-dependent Protease Calpain
J. Biol. Chem.,
April 21, 2006;
281(16):
11260 - 11270.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Marzia, R. Chiusaroli, L. Neff, N.-Y. Kim, A. H. Chishti, R. Baron, and W. C. Horne
Calpain Is Required for Normal Osteoclast Function and Is Down-regulated by Calcitonin
J. Biol. Chem.,
April 7, 2006;
281(14):
9745 - 9754.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Xu and X. Deng
Protein Kinase C{iota} Promotes Nicotine-induced Migration and Invasion of Cancer Cells via Phosphorylation of {micro}- and m-Calpains
J. Biol. Chem.,
February 17, 2006;
281(7):
4457 - 4466.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Franco and A. Huttenlocher
Regulating cell migration: calpains make the cut
J. Cell Sci.,
September 1, 2005;
118(17):
3829 - 3838.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Parnaud, E. Hammar, D. G. Rouiller, and D. Bosco
Inhibition of calpain blocks pancreatic {beta}-cell spreading and insulin secretion
Am J Physiol Endocrinol Metab,
August 1, 2005;
289(2):
E313 - E321.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Yin, Q. Zheng, C. Yan, and B. C. Berk
GIT1 Is a Scaffold for ERK1/2 Activation in Focal Adhesions
J. Biol. Chem.,
July 29, 2005;
280(30):
27705 - 27712.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Pullikuth, E. McKinnon, H.-J. Schaeffer, and A. D. Catling
The MEK1 Scaffolding Protein MP1 Regulates Cell Spreading by Integrating PAK1 and Rho Signals
Mol. Cell. Biol.,
June 15, 2005;
25(12):
5119 - 5133.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Zatz and A. Starling
Calpains and Disease
N. Engl. J. Med.,
June 9, 2005;
352(23):
2413 - 2423.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Ehrenreiter, D. Piazzolla, V. Velamoor, I. Sobczak, J. V. Small, J. Takeda, T. Leung, and M. Baccarini
Raf-1 regulates Rho signaling and cell migration
J. Cell Biol.,
March 14, 2005;
168(6):
955 - 964.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Satish, H. C. Blair, A. Glading, and A. Wells
Interferon-Inducible Protein 9 (CXCL11)-Induced Cell Motility in Keratinocytes Requires Calcium Flux-Dependent Activation of {micro}-Calpain
Mol. Cell. Biol.,
March 1, 2005;
25(5):
1922 - 1941.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. S. Hendriks, G. Orr, A. Wells, H. S. Wiley, and D. A. Lauffenburger
Parsing ERK Activation Reveals Quantitatively Equivalent Contributions from Epidermal Growth Factor Receptor and HER2 in Human Mammary Epithelial Cells
J. Biol. Chem.,
February 18, 2005;
280(7):
6157 - 6169.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Xu and X. Deng
Tobacco-specific Nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Phosphorylation of {micro}- and m-Calpain in Association with Increased Secretion, Cell Migration, and Invasion
J. Biol. Chem.,
December 17, 2004;
279(51):
53683 - 53690.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Sato, S. Hattori, S. Irie, H. Sorimachi, M. Inomata, and S. Kawashima
Degradation of Fodrin by m-Calpain in Fibroblasts Adhering to Fibrillar Collagen I Gel
J. Biochem.,
December 1, 2004;
136(6):
777 - 785.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Inserte, D. Garcia-Dorado, M. Ruiz-Meana, L. Agullo, P. Pina, and J. Soler-Soler
Ischemic preconditioning attenuates calpain-mediated degradation of structural proteins through a protein kinase A-dependent mechanism
Cardiovasc Res,
October 1, 2004;
64(1):
105 - 114.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Ajenjo, E. Canon, I. Sanchez-Perez, D. Matallanas, J. Leon, R. Perona, and P. Crespo
Subcellular Localization Determines the Protective Effects of Activated ERK2 against Distinct Apoptogenic Stimuli in Myeloid Leukemia Cells
J. Biol. Chem.,
July 30, 2004;
279(31):
32813 - 32823.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. T. Eblen, J. K. Slack-Davis, A. Tarcsafalvi, J. T. Parsons, M. J. Weber, and A. D. Catling
Mitogen-Activated Protein Kinase Feedback Phosphorylation Regulates MEK1 Complex Formation and Activation during Cellular Adhesion
Mol. Cell. Biol.,
March 15, 2004;
24(6):
2308 - 2317.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Glading, R. J. Bodnar, I. J. Reynolds, H. Shiraha, L. Satish, D. A. Potter, H. C. Blair, and A. Wells
Epidermal Growth Factor Activates m-Calpain (Calpain II), at Least in Part, by Extracellular Signal-Regulated Kinase-Mediated Phosphorylation
Mol. Cell. Biol.,
March 15, 2004;
24(6):
2499 - 2512.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. Kifor, I. Kifor, F. D. Moore Jr., R. R. Butters Jr., and E. M. Brown
m-Calpain Colocalizes with the Calcium-sensing Receptor (CaR) in Caveolae in Parathyroid Cells and Participates in Degradation of the CaR
J. Biol. Chem.,
August 15, 2003;
278(33):
31167 - 31176.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Mamoune, J.-H. Luo, D. A. Lauffenburger, and A. Wells
Calpain-2 as a Target for Limiting Prostate Cancer Invasion
Cancer Res.,
August 1, 2003;
63(15):
4632 - 4640.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. E. GOLL, V. F. THOMPSON, H. LI, W. WEI, and J. CONG
The Calpain System
Physiol Rev,
July 1, 2003;
83(3):
731 - 801.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. K. Wong, H. H. Le, A. Zsarnovszky, and S. M. Belcher
Estrogens and ICI182,780 (Faslodex) Modulate Mitosis and Cell Death in Immature Cerebellar Neurons via Rapid Activation of p44/p42 Mitogen-Activated Protein Kinase
J. Neurosci.,
June 15, 2003;
23(12):
4984 - 4995.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. M. Carlin, M. Roth, and J. L. Black
Urokinase potentiates PDGF-induced chemotaxis of human airway smooth muscle cells
Am J Physiol Lung Cell Mol Physiol,
June 1, 2003;
284(6):
L1020 - L1026.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Lokuta, P. A. Nuzzi, and A. Huttenlocher
Calpain regulates neutrophil chemotaxis
PNAS,
April 1, 2003;
100(7):
4006 - 4011.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Delmas, N. Aragou, S. Poussard, P. Cottin, J.-M. Darbon, and S. Manenti
MAP Kinase-dependent Degradation of p27Kip1 by Calpains in Choroidal Melanoma Cells. REQUIREMENT OF p27Kip1 NUCLEAR EXPORT
J. Biol. Chem.,
March 28, 2003;
278(14):
12443 - 12451.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. S. Hendriks, L. K. Opresko, H. S. Wiley, and D. Lauffenburger
Coregulation of Epidermal Growth Factor Receptor/Human Epidermal Growth Factor Receptor 2 (HER2) Levels and Locations: Quantitative Analysis of HER2 Overexpression Effects
Cancer Res.,
March 1, 2003;
63(5):
1130 - 1137.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Haugh
Localization of Receptor-Mediated Signal Transduction Pathways: The Inside Story
Mol. Interv.,
September 1, 2002;
2(5):
292 - 307.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Shiraha, A. Glading, J. Chou, Z. Jia, and A. Wells
Activation of m-Calpain (Calpain II) by Epidermal Growth Factor Is Limited by Protein Kinase A Phosphorylation of m-Calpain
Mol. Cell. Biol.,
April 15, 2002;
22(8):
2716 - 2727.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Barbieri, C. M. Heath, E. M. Peters, A. Wells, J. N. Davis, and P. D. Stahl
Phosphatidylinositol-4-phosphate 5-Kinase-1beta Is Essential for Epidermal Growth Factor Receptor-mediated Endocytosis
J. Biol. Chem.,
December 7, 2001;
276(50):
47212 - 47216.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Maheshwari, H. S. Wiley, and D. A. Lauffenburger
Autocrine epidermal growth factor signaling stimulates directionally persistent mammary epithelial cell migration
J. Cell Biol.,
December 24, 2001;
155(7):
1123 - 1128.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|