Cell Responses to Growth Factors: The Role of Receptor Tyrosine Kinase Intracellular Domain Fragments

Growth factor activation of receptor tyrosine kinases (RTKs) provokes well-described canonical second messenger pathways that transmit biochemical signals in the cytoplasm and to the nucleus to initiate cellular responses. The proteolytic liberation of intracellular domain fragments (ICDs) from activated RTKs and the nuclear translocation of these ICDs represent a more recently identified and noncanonical mechanism by which RTKs communicate with the nucleus. Several reports have added previously unknown facets to the ICD mechanism and have enlarged the scope of ICDs as second messengers.