UI - 20548722
AU - Lanzetti L
AU - Rybin V
AU - Malabarba MG
AU - Christoforidis S
AU - Scita G
AU - Zerial M
AU - Di Fiore PP
TI - The Eps8 protein coordinates EGF receptor signalling through Rac and
trafficking through Rab5 [In Process Citation]
LA - Eng
DA - 20001129
DP - 2000 Nov 16
IS - 0028-0836
TA - Nature
PG - 374-7
SB - M
SB - X
IP - 6810
VI - 408
AB - 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.
AD - Department of Experimental Oncology, European Institute of Oncology,
Milan, Italy.
RO - O:099
PMID- 0011099046
MHDA- 2000/12/01 11:00
EDAT- 2000/12/01 11:00
SO - Nature 2000 Nov 16;408(6810):374-7