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| Curr. Biol. Aug (2000); 10(16):1009-12 | |
| Attenuation of EGF receptor signaling by a metastasis suppressor, the tetraspanin CD82/KAI-1. | |
| Odintsova E, Sugiura T, Berditchevski F | |
| CRC Institute for Cancer Studies, The University of Birmingham, Edgbaston, UK. | |
| Abstract: The 'metastasis suppressor' CD82/KAI-1, a member of the tetraspanin superfamily of transmembrane proteins, is widely distributed in normal tissues [1], and has been shown to be suppressed in the advanced stages of various epithelial malignancies [2-6]. Although the physiological relevance of this change is unknown, in vitro data show that ectopically expressed CD82/KAI-1 can suppress tumor cell migration, a process underlying the dissemination of tumor cells in vivo [5]. The function of CD82/KAI-1 is not known and it has been proposed that association of CD82/KAI-1 with other cell-surface proteins may be pivotal in directing its biological activities [7,8]. We show here that the CD82/KAI-1 tetraspanin is directly associated with the EGF receptor (EGFR), and that ectopic expression of CD82/KAI-1 in epithelial cells specifically suppresses EGF-induced lamellipodial extensions and cell migration. In cells expressing CD82/KAI-1, the initial activation of EGFR is not affected, but subsequent desensitization of EGF-induced signaling occurs more rapidly. This attenuation is correlated with an increased rate of receptor endocytosis. These results identify CD82/KAI-1 as a new regulator of EGF-induced signaling and show that the association of EGFR with the tetraspanin is critical in EGFR desensitization. | |
| [PUBMED: 10985391] |   |
| Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |