Structural requirements for b1 integrin cytoplasmic domain functions in adhesion, migration and signaling have been studied mainly for ®broblasts in vitro. The relevance for b1-dependent in vivo migration of lymphoid cells has not been assessed. To study this, we transfected b1 mutants into b1-de®cient double knockout (DKO) ESb lymphoma cells, and tested the capacity of the cells to metastasize to liver and spleen. This was compared to a4b1-dependent invasion into cell monolayers in vitro and Mn
2+-induced adhesion to ®bronectin. Deletion of the ®ve C-terminal residues or mutation of both threonines T788 and T789 to alanines blocked invasion and metastasis and greatly reduced adhesion, in line with known in vitro eects. However, mutations of the NPXY motif tyrosines had unexpected consequences. A Y783F mutation had no eect at all, but a Y783,795F double mutation strongly reduced Mn 2+ -induced adhesion, whereas it had limited eects on invasion and metastasis. Furthermore, cells expressing a b1b2 chimeric subunit, which contains phenylalanines in the NPXY/F motifs, adhered poorly but invasion and metastasis was fully restored to the same levels as for cells expressing wildtype b1. We conclude that part of the functions of the b1 cytoplasmic domain that are required for adhesion are not essential for b1-dependent invasion and metastasis.
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