Back to Search
Start Over
The EIIIA segment of fibronectin is a ligand for integrins alpha 9beta 1 and alpha 4beta 1 providing a novel mechanism for regulating cell adhesion by alternative splicing.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2002 Apr 26; Vol. 277 (17), pp. 14467-74. Date of Electronic Publication: 2002 Feb 11. - Publication Year :
- 2002
-
Abstract
- Alternative splicing of the fibronectin gene transcript gives rise to forms that include the EIIIA (or ED-A) segment. EIIIA-containing fibronectins are prominently expressed during embryogenesis and wound healing and appear to mediate changes in cell adhesion and gene expression. Nonetheless, integrins that bind the EIIIA segment have not been identified. We previously mapped the epitope for two function-blocking monoclonal antibodies to the C-C' loop region of the EIIIA segment (Liao, Y.-F., Wieder, K. G., Classen, J. M., and Van De Water, L. (1999) J. Biol. Chem. 274, 17876-17884). The sequence of this epitope ((39)PEDGIHELFP(48)) resembles the sequence within tenascin-C to which the integrin alpha(9)beta(1) binds. We now report that either integrin alpha(9)beta(1) or alpha(4)beta(1) can mediate cell adhesion to the EIIIA segment. Moreover, this interaction is blocked both by epitope-mapped EIIIA antibodies as well as by the respective anti-integrins. Deletion mutants of the EIIIA segment that include the C-C' loop and flanking sequence bind cells expressing either alpha(9)beta(1) or alpha(4)beta(1). Adhesion of alpha(4)beta(1)-containing MOLT-3 cells to the EIIIA segment stimulates phosphorylation of p44/42 MAP kinase. Our observation that two integrins bind the EIIIA segment establishes a novel mechanism by which cell adhesion to fibronectin is regulated by alternative splicing.
- Subjects :
- Amino Acid Sequence
Fibronectins chemistry
Fibronectins physiology
Humans
Integrin alpha4beta1
Ligands
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases metabolism
Phosphorylation
Sequence Deletion
Tyrosine metabolism
Alternative Splicing
Cell Adhesion physiology
Fibronectins metabolism
Integrins metabolism
Receptors, Lymphocyte Homing metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 277
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11839764
- Full Text :
- https://doi.org/10.1074/jbc.M201100200