{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:59:55Z","timestamp":1792277995302,"version":"4.4.0"},"reference-count":33,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The most prominent cell-surface integrin \u03b14\u03b21 partner, a 70-kDa protein, was isolated from MOLT-4 T leukemia cells, using anti\u2013\u03b14\u03b21 integrin antibody-coated beads. By mass spectrometry, this protein was identified as EWI-2, a previously described cell-surface partner for tetraspanin proteins CD9 and CD81. Wild-type EWI-2 overexpression had no effect on MOLT-4 cell tethering and adhesion strengthening on the \u03b14\u03b21 ligand, vascular cell adhesion molecule-1 (VCAM-1), in shear flow assays. However, EWI-2 markedly impaired spreading and ruffling on VCAM-1. In contrast, a mutant EWI-2 molecule, with a different cytoplasmic tail, neither impaired cell spreading nor associated with \u03b14\u03b21 and CD81. The endogenous wild-type EWI-2\u2013CD81\u2013\u03b14\u03b21 complex was fully soluble, and highly specific as seen by the absence of other MOLT-4 cell-surface proteins. Also, it was relatively small in size (0.5 \u00d7 106 Da to 4 \u00d7 106 Da), as estimated by size exclusion chromatography. Overexpression of EWI-2 in MOLT-4 cells caused reorganization of cell-surface CD81, increased the extent of CD81-CD81, CD81-\u03b14\u03b21, and \u03b14\u03b21-\u03b14\u03b21 associations, and increased the apparent size of CD81-\u03b14\u03b21 complexes. We suggest that EWI-2\u2013dependent reorganization of \u03b14\u03b21-CD81 complexes on the cell surface is responsible for EWI-2 effects on integrin-dependent morphology and motility functions. 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