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J. Biol. Chem., Vol. 275, Issue 30, 22736-22742, July 28, 2000
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From the Department of Vascular Biology, The Scripps Research
Institute, La Jolla, California 92037
Paxillin Binding to a Conserved Sequence Motif in the
4 Integrin Cytoplasmic Domain*
and
4
1
integrin-mediated cell adhesion results in increased cell migration,
reduced cell spreading, and focal adhesion formation relative to other
1 integrins. Paxillin, a signaling adapter protein,
binds tightly to the 4 cytoplasmic domain and is
implicated in 4 integrin signaling. We now report the
mapping of a paxillin-binding site in the 4 cytoplasmic
domain and an assessment of its role in the 4
tail-specific integrin functions. By using truncation mutants and a
peptide competition assay, we found that a region of 9 amino acid
residues (Glu983-Tyr991) within the
4 cytoplasmic domain contains a minimal sequence sufficient for paxillin binding. Alanine scanning of this region implicated Tyr991 and Glu983 as critical
residues. The role of these residues was confirmed by introducing these
Ala substitutions into the full-length 4 tail sequence.
Y991A or E983A substitution disrupted the interaction of
4 integrins with paxillin. These same two point
mutations reversed the effects of the 4 tail on cell
spreading. The key features of the identified paxillin-binding sequence
are present in all 4 integrins sequenced to date,
including that from Xenopus laevis. The maintenance of this
sequence motif suggests that paxillin binding is an evolutionarily
conserved function of 4 integrins.
*
This work was supported in part by grants from the National
Institutes of Health. This is publication number 13010VB from the
Scripps Research Institute.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.
Supported by National Service Research Award IF32HL09922-01.
§
To whom correspondence should be addressed: Dept. of Vascular
Biology, VB-2, The Scripps Research Institute, 10550 N. Torrey Pines
Rd., La Jolla, CA 92037. Tel.: 858-784-7143; Fax: 858-784-7343; E-mail:
ginsberg@scripps.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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