"this" "has MEDLINE Unique Identifier" "20548722"
"this" "authored by" "Lanzetti L"
"this" "authored by" "Rybin V"
"this" "authored by" "Malabarba MG"
"this" "authored by" "Christoforidis S"
"this" "authored by" "Scita G"
"this" "authored by" "Zerial M"
"this" "authored by" "Di Fiore PP"

"EGFR" "is a synonym for" "EGFR"
"Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5"
"Eps8 protein" "coordinates" "EGFR signalling"
"EGFR signalling" "is coordinated via" "Rac protein"
"Eps8 protein" "coordinates" "EGFR trafficking"
"EGFR trafficking" "is coordinated via" "Rab5 protein"
"Eps8 protein" "coordinates signalling of" "EGFR"

"this" "was published" "2000 Nov 16"

"this" "appeared in" "Nature"
"this" "appears on page" "374-7"

"this" "originates in" "ENGLAND"
"this" "has journal issue number" "6810"
"this" "has journal volume number" "408"

AB - How epidermal growth factor receptor (EGFR) signalling is linked to EGFR trafficking is largely unknown.

"EGFR signalling" "is linked to" "EGFR trafficking"

Signalling and trafficking involve small GTPases of the Rho and Rab families,

"small GTPases" "belong to" "Rho protein family"
"small GTPases" "belong to" "Rab protein family"

"EGFR signalling" "involves" "Rho protein family"
"EGFR trafficking" "involves" "Rab protein family"

But it remains unknown whether the signalling relying on these two classes of GTPases is integrated,
if it is,
what molecular machinery is involved.

Here we report that the protein Eps8 connects these signalling pathways.

"Eps8 protein" "is connected to" "EGFR signalling"
"Eps8 protein" "is connected to" "EGFR trafficking"

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.

"Eps8 protein" "is a substrate of" "EGFR"

"E3bl protein" "holds in a complex" "Sos1 protein"
"Sos1 protein" "can complex with" "EGFR"

"Sos1 protein" "can complex with" "Eps8 protein"

"E3bl protein" "is an" "adapter protein"
"E3bl protein" "mediates activation of" "Rac protein"
"EGFR" "complexes with" "Sos1 protein"

Through its src homology-3 domain, Eps8 interacts with RN-tre.

"Eps8 protein" "interacts with" "RN-tre protein"
"Eps8 protein" "is homologous to" "src protein"
"Eps8 protein" "has a homology-3 domain in common with" "src protein"

We show that RN-tre is a Rab5 GTPase-activating protein, whose activity is regulated by the EGFR.

"RN-tre protein" "is a" "Rab5 GTPase-activating protein"
"RN-tre protein" "is regulated by" "EGFR"

By entering in a complex with Eps8, RN-tre acts on Rab5 and inhibits internalization of the EGFR.

"RN-tre protein" "complexes with" "Eps8 protein"
"RN-tre protein" "acts on" "Rab5 protein"
"RN-tre protein" "inhibits internalization of" "EGFR"

Furthermore, RN-tre diverts Eps8 from its Rac-activating function,
resulting in the attenuation of Rac signalling.

"RN-tre protein" "diverts" "Eps8 protein"
"RN-tre protein" "attenuates" "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.

"Eps8 protein" "signals" "EGFR"
"EGFR signalling" "takes place via" "Rac protein"
"EGFR trafficking" "takes place via" "Rab5 protein"

"author" "is affililiated with" "Department of Experimental Oncology",
European Institute of Oncology,
Milan, Italy.

"this" "has PubMed identifier" "0011099046"
"this" "has PubMed identifier" "2000/12/01 11:00"
"this" "added to PubMed database" "2000/12/01 11:00"
"this" "has citation" "Nature 2000 Nov 16;408(6810):374-7"