Figure 2.

Four models for ErbB2 resistance to down-regulation. (A) Internalization of ErbB2 is restricted due to a lack of internalization signals, or because interaction with Cdc37-Hsp90 induces a conformation where internalization signals are hidden; (B) ErbB2 is retained at the plasma membrane due to interaction with proteins like flotillins and possibly other raft components; (C) Expression of ErbB2 inhibits the formation of clathrin-coated pits; (D) Internalization of ErbB2 is not inhibited, but ErbB2 in endosomes recycles rapidly back to the plasma membrane. Interaction with Hsp90 has been suggested to sequester ErbB2 homodimers, but for simplicity only monomeric ErbB2 is drawn in the figure. Different internalization pathways may be involved, but also for simplicity, only clathrin-dependent internalization is illustrated.