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The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5.
- Source :
-
Nature [Nature] 2000 Nov 16; Vol. 408 (6810), pp. 374-7. - Publication Year :
- 2000
-
Abstract
- How epidermal growth factor receptor (EGFR) signalling is linked to EGFR trafficking is largely unknown. Signalling and trafficking involve small GTPases of the Rho and Rab families, respectively. But it remains unknown whether the signalling relying on these two classes of GTPases is integrated, and, if it is, what molecular machinery is involved. Here we report that the protein Eps8 connects these signalling pathways. Eps8 is a substrate of the EGFR, which is held in a complex with Sos1 by the adaptor protein E3bl (ref. 2), thereby mediating activation of Rac. Through its src homology-3 domain, Eps8 interacts with RN-tre. We show that RN-tre is a Rab5 GTPase-activating protein, whose activity is regulated by the EGFR. By entering in a complex with Eps8, RN-tre acts on Rab5 and inhibits internalization of the EGFR. Furthermore, RN-tre diverts Eps8 from its Rac-activating function, resulting in the attenuation of Rac signalling. Thus, depending on its state of association with E3b1 or RN-tre, Eps8 participates in both EGFR signalling through Rac, and trafficking through Rab5.
- Subjects :
- Animals
COS Cells
Carrier Proteins metabolism
Catalysis
Cloning, Molecular
Cytoskeletal Proteins
Endocytosis
GTPase-Activating Proteins
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins
Oncogene Proteins, Fusion metabolism
Protein Binding
Protein Structure, Tertiary
Recombinant Fusion Proteins
SOS1 Protein metabolism
Adaptor Proteins, Signal Transducing
ErbB Receptors metabolism
Proteins physiology
Signal Transduction
rab5 GTP-Binding Proteins metabolism
rac GTP-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0028-0836
- Volume :
- 408
- Issue :
- 6810
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 11099046
- Full Text :
- https://doi.org/10.1038/35042605