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Vol. 12, Issue 10, 2975-2986, October 2001
1 Integrin Function
through Interactions with Integrin 
31
and
*Respiratory Division, Brigham and Women's Hospital, Harvard
Medical School, Boston, Massachusetts 02115; The urokinase receptor (uPAR) is linked to cellular migration
through its capacity to promote pericellular proteolysis, regulate integrin function, and mediate cell signaling in response to
urokinase (uPA) binding. The mechanisms for these activities
remain incompletely defined, although uPAR was recently identified as a
cis-acting ligand for the Department
of Physiological Chemistry, University of Münster, 48149 Münster, Germany; Department of Medicine,
Children's Hospital, and Department of Pediatrics, Harvard Medical
School, Boston, Massachusetts 02115; and §Pulmonary and
Critical Care Division, University of California at San Francisco, San
Francisco, California 94143.
2 integrin
CD11b/CD18 (Mac-1). Here we show that a major 1 integrin
partner for uPAR/uPA signaling is 
3. In uPAR-transfected 293 cells
uPAR complexed (>90%) with 31 and antibodies to 3 blocked
uPAR-dependent vitronectin (Vn) adhesion. Soluble uPAR bound to
recombinant 31 in a uPA-dependent manner
(Kd < 20 nM) and binding was blocked
by a 17-mer 31 integrin peptide (325) homologous to
the CD11b uPAR-binding site. uPAR colocalized with 31 in
MDA-MB-231 cells and uPA (1 nM) enhanced spreading and focal adhesion
kinase phosphorylation on fibronectin (Fn) or collagen type I
(Col) in a pertussis toxin- and 325-sensitive manner. A critical
role of 31 in uPA signaling was verified by studies of epithelial
cells from 3-deficient mice. Thus, uPAR preferentially complexes
with 31, promoting direct (Vn) and indirect (Fn, Col) pathways of
cell adhesion, the latter a heterotrimeric G protein-dependent mechanism of signaling between 31 and other 1 integrins.
Corresponding author: E-mail address:
halchap{at}itsa.ucsf.edu.
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