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2ß1 Integrin
2 Cytoplasmic Domain
From the Department of Pathology and Immunology,*
Washington University School of Medicine, St. Louis, Missouri; and the
Howard Hughes Medical Institute,
Chevy Chase,
Maryland
The 
2ß1 integrin supports cell-cycle
progression of mammary epithelial cells adherent to type I collagen
matrices. Integrin collagen receptors containing the 2
cytoplasmic domain stimulated expression of cyclin E and
cyclin-dependent kinase (cdk)2, resulting in cyclin E/cdk2
activation in the absence of growth factors other than insulin.
Integrin collagen receptors in which the 2 cytoplasmic
domain was replaced by the 1 cytoplasmic domain or an
2 subunit cytoplasmic domain truncated after the GFFKR
sequence failed to stimulate cyclin E/cdk2 activation or entry into S
phase in the absence of growth factors. Although overexpression of
cyclins D or E or cdk2 in cells expressing the integrin collagen
receptor with the 1-integrin cytoplasmic domain did not
restore G1 progression when mammary epithelial cells
adhered to type I collagen, co-expression of cyclin E and cdk2
did rescue the ability of the transfectants to enter S phase.
Activation of cyclin E/cdk2 complex by mammary epithelial cells
required synergy between adhesion mediated by an integrin collagen
receptor containing the 2-integrin subunit cytoplasmic
domain and the insulin receptor.
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