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MBC in Press, published online ahead of print October 5, 2005
Mol. Biol. Cell 10.1091/mbc.E05-05-0456

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Submitted on May 24, 2005
Revised on September 13, 2005
Accepted on September 23, 2005

The Inhibitory Effect of ErbB2 on EGF-induced Formation of Clathrin-coated Pits Correlates with Retention of EGFR-ErbB2 Oligomeric Complexes at the Plasma Membrane

Camilla Haslekås,* Kamilla Breen,* Ketil W. Pedersen, Lene Johannessen, Espen Stang, and Inger Helene Madshus

Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo, Norway

Monitoring Editor: Jean Gruenberg

By constructing stably transfected cells harboring the same amount of Epidermal Growth Factor (EGF) receptor (EGFR), but with increasing overexpression of ErbB2, we have demonstrated that ErbB2 efficiently inhibits internalization of ligand-bound EGFR. Apparently, ErbB2 inhibits internalization of EGF-bound EGFR by constitutively driving EGFR-ErbB2 hetero/oligomerization. We have demonstrated that ErbB2 does not inhibit phosphorylation or ubiquitination of the EGFR. Our data further indicate that the endocytosis deficiency of ErbB2 and of ErbB2-EGFR heterodimers/oligomers cannot be explained by anchoring of ErbB2 to PDZ-containing proteins like Erbin. Instead, we demonstrate that in contrast to EGFR homodimers, which are capable of inducing new clathrin-coated pits in serum-starved cells upon incubation with EGF, clathrin-coated pits are not induced upon activation of EGFR-ErbB2 heterodimers/oligomers.

*These authors contributed equally to this work.

Address correspondence to: Inger Helene Madshus (i.h.madshus{at}medisin.uio.no)




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