Abstract
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 assays using bacterially expressed proteins. Immunofluorescent studies performed in L6 myoblasts expressing both native and epitope-tagged 16K demonstrate 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 prominent staining in focal adhesions. This helix is also required for ligand-independent activation of platelet-derived growth factor-beta 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.
Highlights
Integrins comprise the major family of cell surface receptor proteins that interact with the extracellular matrix (ECM)1 or with counter receptors on adjacent cells
Overexpression of 16kDa subunit of vacuolar H؉-ATPase (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
Integrin receptors involved in ECM interactions cluster at the points where stable binding to the matrix occurs, producing “focal adhesions” to which cytoskeletal components and signaling molecules co-localize [4, 5]
Summary
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 required for ligand-independent activation of plateletderived growth factor- receptor signaling by the human papillomavirus E5 oncoprotein. 16K is composed of four hydrophobic regions thought to form transmembrane ␣-helices, and plays a key role in the assembly and function of the V-ATPase pump [26] It comprises structures independently of the V-ATPase, including gap junctional complexes and mediatophores, which are involved in the release of neurotransmitters [27,28,29,30]. 16K utilizes transmembrane interactions with receptors to shuttle them through the cell and to cell membranes
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