spacer gif spacer gif spacer gif spacer gif Propose a workshop for 2011 spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 14 Aug 2007
doi: 10.1242/jcs.005298

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.005298v1
120/17/3138    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yip, S.-C.
Right arrow Articles by Backer, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yip, S.-C.
Right arrow Articles by Backer, J. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

The distinct roles of Ras and Rac in PI 3-kinase-dependent protrusion during EGF-stimulated cell migration


Shu-Chin Yip, Mirvat El-Sibai, Salvatore J. Coniglio, Ghassan Mouneimne, Robert J. Eddy, Beth E. Drees, Paul O. Neilsen, Sumanta Goswami, Marc Symons, John S. Condeelis, and Jonathan M. Backer*
* Author for correspondence (e-mail: backer{at}aecom.yu.edu)

Cell migration involves the localized extension of actin-rich protrusions, a process that requires Class I phosphoinositide 3-kinases (PI 3-kinases). Both Rac and Ras have been shown to regulate actin polymerization and activate PI 3-kinase. However, the coordination of Rac, Ras and PI 3-kinase activation during epidermal growth factor (EGF)-stimulated protrusion has not been analyzed. We examined PI 3-kinase-dependent protrusion in MTLn3 rat adenocarcinoma cells. EGF-stimulated phosphatidy_l_inositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] levels showed a rapid and persistent response, as PI 3-kinase activity remained elevated up to 3 minutes. The activation kinetics of Ras, but not Rac, coincided with those of leading-edge PtdIns(3,4,5)P3 production. Small interfering RNA (siRNA) knockdown of K-Ras but not Rac1 abolished PtdIns(3,4,5)P3 production at the leading edge and inhibited EGF-stimulated protrusion. However, Rac1 knockdown did inhibit cell migration, because of the inhibition of focal adhesion formation in Rac1 siRNA-treated cells. Our data show that in EGF-stimulated MTLn3 carcinoma cells, Ras is required for both PtdIns(3,4,5)P3 production and lamellipod extension, whereas Rac1 is required for formation of adhesive structures. These data suggest an unappreciated role for Ras during protrusion, and a crucial role for Rac in the stabilization of protrusions required for cell motility.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. A. Antonyak, B. Li, A. D. Regan, Q. Feng, S. S. Dusaban, and R. A. Cerione
Tissue Transglutaminase Is an Essential Participant in the Epidermal Growth Factor-stimulated Signaling Pathway Leading to Cancer Cell Migration and Invasion
J. Biol. Chem., July 3, 2009; 284(27): 17914 - 17925.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
H.-D. Kim, T. W. Guo, A. P. Wu, A. Wells, F. B. Gertler, and D. A. Lauffenburger
Epidermal Growth Factor-induced Enhancement of Glioblastoma Cell Migration in 3D Arises from an Intrinsic Increase in Speed But an Extrinsic Matrix- and Proteolysis-dependent Increase in Persistence
Mol. Biol. Cell, October 1, 2008; 19(10): 4249 - 4259.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
C. Sarmiento, W. Wang, A. Dovas, H. Yamaguchi, M. Sidani, M. El-Sibai, V. DesMarais, H. A. Holman, S. Kitchen, J. M. Backer, et al.
WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells
J. Cell Biol., March 24, 2008; 180(6): 1245 - 1260.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
V. Kolsch, P. G. Charest, and R. A. Firtel
The regulation of cell motility and chemotaxis by phospholipid signaling
J. Cell Sci., March 1, 2008; 121(5): 551 - 559.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
M. Sidani, D. Wessels, G. Mouneimne, M. Ghosh, S. Goswami, C. Sarmiento, W. Wang, S. Kuhl, M. El-Sibai, J. M. Backer, et al.
Cofilin determines the migration behavior and turning frequency of metastatic cancer cells
J. Cell Biol., November 19, 2007; 179(4): 777 - 791.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. El-Sibai, P. Nalbant, H. Pang, R. J. Flinn, C. Sarmiento, F. Macaluso, M. Cammer, J. S. Condeelis, K. M. Hahn, and J. M. Backer
Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells
J. Cell Sci., October 1, 2007; 120(19): 3465 - 3474.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2007