The ErbB receptors are tyrosine kinases that bind a wide variety of ligands. They are implicated in cell proliferation, generation of anti-apoptotic signals, differentiation, and cell migration. The over-expression of different ErbB receptors and/or the expression of aberrant mutant forms are responsible for the development of many human cancers. A simplified view of the mechanism of action of these receptors is that they are triggered when located at the cell surface and/or when present in endosomes. In this review we will discuss a newly emergent, and more complex, picture in which ErbB receptors and their ligands translocate to the cell nucleus where they assume additional functions. The possible involvement of calmodulin in the translocation process will be discussed, as well. The development of new therapeutic strategies targeting the nuclear translocation system and/or the nuclear functions of ErbB receptors could help to control the rapid growth of certain types of tumor cells.

The work in the authors laboratory was financed by grants (to AV) from the Comisión Interministerial de Ciencia y Tecnología (SAF2002-03258), the Consejería de Educación de la Comunidad de Madrid (08.1/0027/2001-1), and the Agencia Española de Cooperación Internacional (2002CN0013). The generous support of the Instituto Carlos III, Fondo de Investigaciones Sanitarias (RTICCC C03/10) is also acknowledged.

Peer Reviewed