Distinct Regions of the Cadherin Cytoplasmic Domain Are Essential for Functional Interaction with Gα12 and β-Catenin
Heterotrimeric G proteins of the G12 subfamily mediate cellular signals leading to events such as cytoskeletal rearrangements, cell proliferation, and oncogenic transformation. Several recent studies have revealed direct effector proteins through which G12 subfamily members may transmit signals lead...
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Published in | The Journal of biological chemistry Vol. 276; no. 47; pp. 44037 - 44043 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
23.11.2001
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Online Access | Get full text |
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Summary: | Heterotrimeric G proteins of the G12 subfamily mediate cellular signals leading to events such as cytoskeletal rearrangements, cell proliferation, and oncogenic transformation. Several recent studies have revealed direct effector proteins through which G12 subfamily members may transmit signals leading to various cellular responses. Our laboratory recently demonstrated that Gα12 and Gα13specifically interact with the cytoplasmic domains of several members of the cadherin family of cell adhesion molecules (Meigs, T. E., Fields, T. A., McKee, D. D., and Casey, P. J. (2001)Proc. Natl. Acad. Sci. U. S. A. 98, 519–524). This interaction causes β-catenin to release from cadherin and relocalize to the cytoplasm and nucleus, where it participates in transcriptional activation. Here we report that two distinct regions of the epithelial cadherin (E-cadherin) tail are required for interaction with β-catenin and Gα12, respectively. Deletion of an acidic, 19-amino acid region of E-cadherin abolishes its ability to bind β-catenin in vitro, to inhibit β-catenin-mediated transactivation, or to stabilize β-catenin; causes subcellular mislocalization of β-catenin; and disrupts cadherin-mediated cell adhesion. On the other hand, deletion of a distinct 11-amino acid region of E-cadherin dramatically attenuates interaction with Gα12; furthermore, Gα12 is ineffective in stimulating β-catenin release from an E-cadherin cytoplasmic domain lacking this putative Gα12-binding region. These findings indicate that Gα12 and β-catenin do not compete for the same binding site on cadherin and provide molecular targets for selectively disrupting the interaction of these proteins with cadherin. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M106121200 |