The conventional view of receptor tyrosine kinase-mediated signal transduction holds that upon ligand binding, a signaling cascade initiated at the cell surface ultimately regulates gene expression. Although it has been proposed that such receptors may localize to the nucleus to affect transcription directly, the mechanism for nuclear translocation has not been clear. Ni et al. (see the Perspective by Heldin and Ericsson) show that cleavage of ErbB-4, an epidermal growth factor receptor family member, by presenilin-dependent secretase releases a transcriptionally active intracellular domain of ErbB-4 to the nucleus. In the absence of this cleavage, the ErbB-4 ligand could not modulate cell growth.
C.-Y. Ni, M. P. Murphy, T. E. Golde, G. Carpenter, γ-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 294, 2179-2181 (2001). [Online Journal]
C.-H. Helden, J. Ericsson, RIPping tyrosine kinase receptors apart. Science 294, 2111-2113 (2001). [Online Journal]