beta(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

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 beta(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 assa ys using bacterially expressed proteins. Immunofluorescent studies performe d in L6 myoblasts ex pressing both native and epitope-tagged 16K demonstrat e co-localization with beta(1) integrin in focal adhesions. Deletion of the fourth of four transmembrane helices in 16K results in loss of interaction with beta(1) integrin in vitro and in the two-hybrid system, and less prom inent staining in focal adhesions. This helix is also required for ligand-i ndependent activation of platelet-derived growth factor-beta receptor signa ling by the human papillomavirus E5 oncoprotein. Overexpression of 16K or e xpression 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 m ight play in integrin movement.