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J Biol Chem, Vol. 274, Issue 33, 23119-23127, August 13, 1999
1 Integrin Binds the 16-kDa Subunit of Vacuolar
H+-ATPase at a Site Important for Human Papillomavirus E5
and Platelet-derived Growth Factor Signaling
Mhairi A.
Skinner and
Alan G.
Wildeman
From the Department of Molecular Biology and Genetics, University
of Guelph, Guelph, Ontario N1G 2W1, Canada
Integrins mediate adhesive interactions between
cells and the extracellular matrix, and play a role in cell migration,
proliferation, differentiation, cytoskeletal organization, and signal
transduction. We have identified an interaction between the
1 integrin and the 16-kDa subunit of vacuolar
H+-ATPase (16K). This interaction was first isolated in a
yeast two-hybrid screen and confirmed by coimmunoprecipitation and in in vitro binding assays using bacterially expressed
proteins. Immunofluorescent studies performed in L6 myoblasts
expressing both native and epitope-tagged 16K demonstrate
co-localization with 1 integrin in focal adhesions.
Deletion of the fourth of four transmembrane helices in 16K results in
loss of interaction with 1 integrin in vitro
and in the two-hybrid system, and less prominent staining in focal
adhesions. This helix is also required for ligand-independent
activation of platelet-derived growth factor- receptor signaling by
the human papillomavirus E5 oncoprotein. Overexpression of 16K or
expression of 16K lacking this helix alters the morphology of myoblasts
and fibroblasts, suggesting that the interaction of 16K with integrins
could be important for cell growth control. We also discuss the
possible role 16K might play in integrin movement.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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