Abstract
Receptor tyrosine kinases (RTKs) were believed until recently to act at the cell membrane in a singular fashion (i.e., binding of ligands on the extracellular domain would activate the intrinsic tyrosine kinase activity in the intracellular domain), which would then start a cascade involving other intracellular signaling molecules that would act as effectors. However, new evidence indicates that some RTKs can signal through a different modality; they can move into the nucleus where they directly exert their actions. Although some studies have showed that the proteolytically released intracellular domain of several RTKs can move to the nucleus where they influence gene expression and cell function, others suggest that RTKs can also move to the nucleus as holoproteins. The identification of this novel signaling mechanism calls for a critical reevaluation of the mechanisms of action of RTKs and their biological roles.