HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 22, 22893-22901, May 28, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/22/22893    most recent M309693200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gustavsson, A. Articles by Fällman, M. Search for Related Content PubMed PubMed Citation Articles by Gustavsson, A. Articles by Fällman, M. Social Bookmarking                      What's this?

Temporal Dissection of ₁-Integrin Signaling Indicates a Role for p130Cas-Crk in Filopodia Formation^*

Anna Gustavsson, Ming Yuan, and Maria Fällman

From the Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden

Invasin-promoted spreading of ₁-integrin-deficient cells, transfected with the _1A- or _1B-integrin splice variants, were used to dissect early ₁-integrin signaling events. The _1B isoform, which has a different membrane-distal part of the cytoplasmic tail from _1A, is defective in signaling and function. When plated on surfaces coated with the high affinity ligand invasin, _1B-integrin-expressing cells spread by forming filopodia with distinct adhesive phosphotyrosine complexes at the tips, without signs of lamellipodia. This suggested that the _1B-integrin mediated a partial signaling sufficient for formation of filopodia but insufficient for lamellipodia formation. When screening for proteins present in the distal filopodial phosphotyrosine complexes of _1B cells, p130Cas and the filopodia proteins vasodilator-stimulated phosphoprotein and talin were found, whereas the typical focal complex proteins focal adhesion kinase, paxillin, and vinculin were not. Invasin-promoted adhesion induced complex formation of p130Cas and the adapter Crk. Moreover, Crk together with Dock180 were present at the filopodial tips of _1B-integrin-expressing cells, and there was a prominent Rac1 activation. Expression of dominant negative variants of p130Cas or CrkII blocked _1B-integrin-mediated filopodia formation, indicating that this signaling scaffold is central in this process.

Received for publication, September 2, 2003 , and in revised form, March 2, 2004.

^* This work was supported by the Swedish Research Council, the Swedish Cancer Foundation, the King Gustavs Vth 80 year Foundation, the Medical Faculty Research Foundation at Umeå University and the Infection and Vaccinology Research Program of the Swedish Foundation for Strategic Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains four additional figures.

Recipient of stipends from the J. C. Kempe Memorial Foundation and from the Wallenberg foundation.

To whom correspondence should be addressed. Tel.: 46-90-7856725; Fax: 46-90-772630; E-mail: maria.fallman{at}molbiol.umu.se.

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

This article has been cited by other articles:

				S. K. Gupta and N. E. Vlahakis Integrin {alpha}9{beta}1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase J. Cell Sci., June 15, 2009; 122(12): 2043 - 2054. [Abstract] [Full Text] [PDF]

				H. Shiratsuchi, Y. Kouatli, G. X. Yu, H. M. Marsh, and M. D. Basson Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation Am J Physiol Cell Physiol, June 1, 2009; 296(6): C1400 - C1410. [Abstract] [Full Text] [PDF]

				A. G. Dupuy and E. Caron Integrin-dependent phagocytosis - spreading from microadhesion to new concepts J. Cell Sci., June 1, 2008; 121(11): 1773 - 1783. [Abstract] [Full Text] [PDF]

				L. M. Stuart, S. A. Bell, C. R. Stewart, J. M. Silver, J. Richard, J. L. Goss, A. A. Tseng, A. Zhang, J. B. E. Khoury, and K. J. Moore CD36 Signals to the Actin Cytoskeleton and Regulates Microglial Migration via a p130Cas Complex J. Biol. Chem., September 14, 2007; 282(37): 27392 - 27401. [Abstract] [Full Text] [PDF]

				M. J. Jarzynka, B. Hu, K.-M. Hui, I. Bar-Joseph, W. Gu, T. Hirose, L. B. Haney, K. S. Ravichandran, R. Nishikawa, and S.-Y. Cheng ELMO1 and Dock180, a Bipartite Rac1 Guanine Nucleotide Exchange Factor, Promote Human Glioma Cell Invasion Cancer Res., August 1, 2007; 67(15): 7203 - 7211. [Abstract] [Full Text] [PDF]

				J. A. Lunn, R. Jacamo, and E. Rozengurt Preferential Phosphorylation of Focal Adhesion Kinase Tyrosine 861 Is Critical for Mediating an Anti-apoptotic Response to Hyperosmotic Stress J. Biol. Chem., April 6, 2007; 282(14): 10370 - 10379. [Abstract] [Full Text] [PDF]

				Y. Makino, M. Tsuda, S. Ichihara, T. Watanabe, M. Sakai, H. Sawa, K. Nagashima, S. Hatakeyama, and S. Tanaka Elmo1 inhibits ubiquitylation of Dock180. J. Cell Sci., March 1, 2006; 119(Pt 5): 923 - 932. [Abstract] [Full Text] [PDF]

				N. Meller, S. Merlot, and C. Guda CZH proteins: a new family of Rho-GEFs J. Cell Sci., November 1, 2005; 118(21): 4937 - 4946. [Abstract] [Full Text] [PDF]