Gαs promotes EEA1 endosome maturation and shuts down proliferative signaling through interaction with GIV (Girdin)
| Autor: | Mikel Garcia-Marcos, Lien T. Nguyen, Anthony Beas, Carmen Teodorof, Vanessa Taupin, Marilyn G. Farquhar |
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| Rok vydání: | 2012 |
| Předmět: |
Gs alpha subunit
Endosome Endocytic cycle Vesicular Transport Proteins Endosomes Biology EEA1 03 medical and health sciences 0302 clinical medicine Heterotrimeric G protein Chlorocebus aethiops Animals Humans RNA Small Interfering Molecular Biology Protein kinase B 030304 developmental biology Adaptor Proteins Signal Transducing Cell Proliferation 0303 health sciences Microfilament Proteins Signal transducing adaptor protein Cell Biology Articles Heterotrimeric GTP-Binding Proteins Signaling Cell biology ErbB Receptors Cell Transformation Neoplastic COS Cells Signal transduction 030217 neurology & neurosurgery HeLa Cells Signal Transduction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 |
| Popis: | EEA1 endosomes are believed to function mainly in down-regulating EGFR signaling, and APPL endosomes are regarded as signaling endosomes. Evidence is given that EGF-induced, proliferative signaling occurs from EEA1 endosomes and is regulated by interaction between the signal-transducing protein GIV and the trimeric G protein Gαs. The organization of the endocytic system into biochemically distinct subcompartments allows for spatial and temporal control of the strength and duration of signaling. Recent work has established that Akt cell survival signaling via the epidermal growth factor receptor (EGFR) occurs from APPL early endosomes that mature into early EEA1 endosomes. Less is known about receptor signaling from EEA1 endosomes. We show here that EGF-induced, proliferative signaling occurs from EEA1 endosomes and is regulated by the heterotrimeric G protein Gαs through interaction with the signal transducing protein GIV (also known as Girdin). When Gαs or GIV is depleted, activated EGFR and its adaptors accumulate in EEA1 endosomes, and EGFR signaling is prolonged, EGFR down-regulation is delayed, and cell proliferation is greatly enhanced. Our findings define EEA1 endosomes as major sites for proliferative signaling and establish that Gαs and GIV regulate EEA1 but not APPL endosome maturation and determine the duration and strength of proliferative signaling from this compartment. |
| Databáze: | OpenAIRE |
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