Reduced cell adhesion during mitosis by threonine phosphorylation of β1 integrin

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Abstract
Cell shape and adhesion of cultured mammalian cells change dramatically during mitosis, however, how cell cycle-dependent alterations in cell adhesion are regulated remain to be elucidated. We show here that normal human mammary epithelial (HME) cells which became less adhesive and adopted the rounded morphology during the G2/M phase of the cell cycle significantly reduced their dependence on β1 integrin-mediated adhesion to laminin, by using function blocking antibody to β1 integrin. In G2/M cells, both total and cell surface expressions of β1 integrin were comparable with those in G1 cells but it was phosphorylated at threonines 788–789 within its cytoplasmic domain and coimmunoprecipitated Ca2+/calmodulin-dependent protein kinase (CaMK) II. The threonine phosphorylated β1 integrin significantly reduced its intracellular linkage with actin, with no significant reduction in the actin expression. In contrast, β1 integrin in G1 cells was not threonine phosphorylated but formed a link with actin and coimmunoprecipitated the core enzyme of the serine/threonine protein phosphatase (PP) 2A. The results suggest that reduced β1 integrin-mediated cell adhesion of HME cells to the substratum during mitosis may be induced by β1 integrin phosphorylation at threonines 788–789 and its reduced ability to link with the actin cytoskeleton. J. Cell. Physiol. 197: 297–305, 2003.