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Titolo:
ROLE OF THE REGULATORY DOMAIN OF THE EGF-RECEPTOR CYTOPLASMIC TAIL INSELECTIVE BINDING OF THE CLATHRIN-ASSOCIATED COMPLEX AP-2
Autore:
BOLL W; GALLUSSER A; KIRCHHAUSEN T;
Indirizzi:
HARVARD UNIV,SCH MED,DEPT CELL BIOL,200 LONGWOOD AVE BOSTON MA 02115 HARVARD UNIV,SCH MED,DEPT CELL BIOL BOSTON MA 02115 HARVARD UNIV,SCH MED,CTR BLOOD RES BOSTON MA 02115
Titolo Testata:
Current biology
fascicolo: 10, volume: 5, anno: 1995,
pagine: 1168 - 1178
SICI:
0960-9822(1995)5:10<1168:ROTRDO>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPIDERMAL GROWTH-FACTOR; PROTEIN-TYROSINE KINASE; LIGAND-INDUCED INTERNALIZATION; COATED PIT FORMATION; ASSEMBLY POLYPEPTIDES; SELF-PHOSPHORYLATION; MEDIATED ENDOCYTOSIS; INVITRO BINDING; VESICLES; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
W. Boll et al., "ROLE OF THE REGULATORY DOMAIN OF THE EGF-RECEPTOR CYTOPLASMIC TAIL INSELECTIVE BINDING OF THE CLATHRIN-ASSOCIATED COMPLEX AP-2", Current biology, 5(10), 1995, pp. 1168-1178

Abstract

Background: After stimulation of a cell by the mitogenic epidermal growth factor (EGF), the EGF receptor (EGF-R) is cleared from the cell surface in order to turn off receptor signaling. This internalization is mediated via clathrin-coated pits and coated vesicles, and ultimately the receptors are delivered to the lysosome and destroyed. It is believed that clathrin-associated protein complexes or adaptors (APs) link che entrapment of EGF-R and other nutrient and growth-factor receptors to the formation of the clathrin-coated pit. Two classes of APs areknown - AP-2, found at the plasma membrane, and AP-1, found in the trans-Golgi network. Activated EGF-R associates with AP-2s at the plasmamembrane, but the mechanism responsible for this association is not known. Here, we investigate, in vivo and in vitro, three aspects of theinteraction between APs and EGF-R: firstly, we ask whether EGF-R at the plasma membrane distinguishes between AP-I and AP-2; secondly, we ask which part of the receptor's cytoplasmic tail is responsible for binding; finally, we ask whether autophosphorylation by EGF-R is essential for the interaction. Results: We demonstrate that EGF-R displays a selective association for AP-2 over AP-1 in vivo, and that this preferential interaction can also be detected using surface plasmon resonance in vitro. Using a truncated mutant and a kinase-dead mutant of EGF-R, we show that the regulatory domain of the cytoplasmic tail is essential For the recruitment of AP-2 in vivo and that this domain is required for association between purified AP-2 and EGF-R in vitro. Finally, we demonstrate, in vivo and in vitro, that tyrosine auto-phosphorylation by the receptor is not an essential pre-condition for the recruitment of AP-2. Conclusions: EGF-R binds selectively to AP-2s, and the regulatory domain of its cytoplasmic tail is required for this interaction. The lack of correlation between receptor autophosphorylation and AP-2 recruitment suggests that activation of the EGF-R kinase stimulatesendocytosis by the phosphorylation of a factor distinct From EGF-R itself as also proposed by others based on experiments measuring receptor traffic and entrapment.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 13:02:21