The EIIIA Segment of Fibronectin Is a Ligand for Integrins α9β1 and α4β1Providing a Novel Mechanism for Regulating Cell Adhesion by Alternative Splicing*
By Y. Liao, P. Gotwals, V. Koteliansky, D. Sheppard, L. Van De Water. Journal of Biological Chemistry, 2002
150 citations recorded by the source corpus.
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 (39PEDGIHELFP48) resembles the sequence within tenascin-C to which the integrin α9β1binds. We now report that either integrin α9β1 or α4β1can 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 α9β1 or α4β1. Adhesion of α4β1-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.
Subfields: Cell Biology, Immunology, Immunology and Allergy
View Paper: https://www.semanticscholar.org/paper/9029a96ae7da07ffae89cf6cb384672fdb18971e
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Citations in the corpus
- Fibronectin at a glance (2002, background): “Recently, binding of α4β1 as well as α9β1 to an EDGIHEL sequence located within the alternatively spliced EDA segment has been reported, suggesting a possible adhesive function for the increased EDA-containing FN species observed during wound healing (Liao et al., 2002).”