Alternative splicing of the integrin β1 subunit mRNA generates a variant form, β1C, with a unique cytoplasmic domain that differs from β1, for a 48-amino acid COOH-terminal sequence. The potential role of this unique sequence in modulating cellular functions was investigated using Chinese hamster ovary (CHO)1 cells transiently transfected with cDNAs coding for human integrin β1C or β1 subunits or mutants containing truncated forms of the β1C cytoplasmic domain. A differential effect of β1C and β1 on cell proliferation was observed. Expression of wild type β1 was associated with a 6-10-fold increase in cell proliferation in response to serum, as measured by [3H]thymidine incorporation. In contrast, only a 2-fold increase in cell proliferation was observed in transfectants expressing comparable levels of β1C. Cells expressing the β1C mutant truncated at Leu794 and lacking the last 31 amino acids of the cytoplasmic domain showed a 12-fold proliferation increase in response to serum. However, three β1C deletion mutants, lacking the COOH-terminal 23, 13, and 8 amino acids, which all contained residues Gln795-Gln802 of the variant cytoplasmic domain responded to serum stimulation with a 2-fold increase in [3H]thymidine uptake. The effect of β1C expression on cell proliferation was not associated with changes in exposure of integrin functional epitopes, as judged by the finding that CHO transfectants expressing β1C, full-length or deletion mutants, or β1 equally adhered to a functionally inhibitory monoclonal antibody against human β1 integrin. Expression of β1C inversely correlated with the mitogenic potential of vascular cells. Absent on growing cultured endothelial cells, surface expression of β1C was induced in growth-arrested, tumor necrosis factor-stimulated endothelial cells. These findings suggest that integrin alternative splicing may provide an accessory mechanism to modulate cell type-specific growth regulatory pathways during vascular cell injury in vivo.
CITATION STYLE
Fornaro, M., Zheng, D. Q., & Languino, L. R. (1995). The novel structural motif Gln795-Gln802 in the integrin β1C cytoplasmic domain regulates cell proliferation. Journal of Biological Chemistry, 270(42), 24666–24669. https://doi.org/10.1074/jbc.270.42.24666
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