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Vol. 12, Issue 10, 3214-3225, October 2001
9 Subunit
Requires the Adaptor Protein Paxillin to Inhibit Cell Spreading but
Promotes Cell Migration in a Paxillin-independent Manner
and
*Lung Biology Center, Department of Medicine, University of
California, San Francisco, San Francisco, California 94110;
The integrin Department of Vascular Biology, Scripps Research
Institute, La Jolla, California 92037; §Department of
Internal Medicine, Department of Laboratory Medicine, National
Hiroshima Hospital, 513 Jike, Saijoh, Higashi-Hiroshima, 739; and
Cancer Biology Program, Division of Hematology-Oncology,
Department of Medicine, Beth Israel Deaconess Medical Center and
Harvard Medical School, Boston, Massachusetts 02215
9 subunit forms a single heterodimer,
9
1. The 9 subunit is most closely related to the 4 subunit,
and like 4 integrins, 91 plays an important role in
leukocyte migration. The 4 cytoplasmic domain preferentially
enhances cell migration and inhibits cell spreading, effects that
depend on interaction with the adaptor protein, paxillin. To determine
whether the 9 cytoplasmic domain has similar effects, a series of
chimeric and deleted 9 constructs were expressed in Chinese hamster
ovary cells and tested for their effects on migration and spreading on
an 91-specific ligand. Like 4, the 9 cytoplasmic domain enhanced cell migration and inhibited cell spreading. Paxillin also
specifically bound the 9 cytoplasmic domain and to a similar level
as 4. In paxillin
/ cells, 9 failed
to inhibit cell spreading as expected but surprisingly still enhanced
cell migration. Further, mutations that abolished the 9-paxillin
interaction prevented 9 from inhibiting cell spreading but had no
effect on 9-dependent cell migration. These findings suggest that
the mechanisms by which the cytoplasmic domains of integrin subunits enhance migration and inhibit cell spreading are distinct and
that the 9 and 4 cytoplasmic domains, despite sequence and
functional similarities, enhance cell migration by different
intracellular signaling pathways.
These authors contributed equally to the work.
¶
Corresponding author. E-mail
address:deans{at}itsa.ucsf.edu.
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