Differential Effects of the Integrins α9β1, αvβ3, and αvβ6 on Cell Proliferative Responses to Tenascin
ROLES OF THE β SUBUNIT EXTRACELLULAR AND CYTOPLASMIC DOMAINS*
- From the ‡ Lung Biology Center, Center for Occupational and Environmental Health, Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, San Francisco, California 94143
- ∥To whom reprint requests and correspondence should be addressed: Lung Biology Center, UCSF Box 0854, San Francisco, CA 94143. Tel.: 415-206-5901; Fax: 415-206-4123.
Abstract
Members of the integrin family manifest considerable overlap in ligand specificity, and many cells have the capacity to express multiple integrin receptors for the same ligand. For example, at least 5 different integrins recognize tenascin as a ligand, and 4 of these bind to the same region of the protein, the third fibronectin type III repeat (TNfn3). We utilized colon carcinoma cells (SW480) that do not normally attach to TNfn3 to examine the possibility that ligation of different integrin receptors for this ligand would induce different effects on cell behavior and intracellular signaling. Heterologous expression of the tenascin receptors αvβ3 and α9β1 produced comparable effects on cell adhesion and spreading on TNfn3, but αvβ3-transfectants proliferated considerably better on each concentration examined. αvβ6-transfectants attached (although less avidly), but completely failed to spread or proliferate. Expression of a chimeric β subunit composed of the β3 extracellular domain fused to the β6 transmembrane and cytoplasmic domains resulted in adhesion and spreading similar to that seen with β3-transfectants, but considerably less proliferation. When the same cell lines were plated on fibronectin, αvβ6-transfectants spread and proliferated as well as cells transfected with the chimeric β3/β6 subunit, but, again, neither cell line proliferated as well as cells expressing αvβ3. Cell proliferation was always associated with spreading and with phosphorylation of the focal adhesion kinase, paxillin, and the mitogen-activated kinase, Erk2, but cell attachment in the absence of spreading or proliferation was not associated with phosphorylation of any of these proteins. These data suggest that different integrin receptors for a single ligand can produce markedly different effects on cell proliferation, and that both the extracellular and cytoplasmic domains of integrin β subunits contribute to these differences.
Footnotes
-
↵¶ Contributed equally to the results reported in this work.
-
↵* This work was supported in part by National Institutes of Health Grants HL/A133259, HL47412, and HL53949 (to D. S.). 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.
-
↵1 The abbreviations used are:
- TNfn3
-
third fibronectin type III repeat
- DMEM
-
Dulbecco's modified Eagle's medium
- PBS
-
phosphate-buffered saline
- BSA
-
bovine serum albumin
- PAGE
-
polyacrylamide gel electrophoresis.
-
↵2Y. Yokosaki, H. Monis, J. Chen, and D. Sheppard, unpublished observations.
-
- Received February 9, 1996.
- Revision received June 4, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
