Abstract
Cells are constantly exposed to various extracellular signals, which coordinate their growth, proliferation, differentiation, mortality and survival. Receptor tyrosine kinases (RTKs) are critical mediators between ligands and cell interior. Such receptors include EGF, PDGF, FGF, HGF, IGF, NGF, VEGF and M-CSF receptors. Immediately following activation of RTKs, these receptors are rapidly translocated from cell surface into the endosomal compartment. Then, these are sorted into lysosomes for degradation.Recently, evidence is accumulating that numerous adaptor proteins are involved in RTKs downregulation by internalization and endocytosis. For example, we have been interested in the role of Cbl (Casitas B-lineage lymphoma) that is a multi-adaptor protein with E3 ubiquitin ligase activity and mediate ubiquitylation of active RTK. We have identified that polyubiquitylation of EGF receptor by Cbl ligase is essential for its internalization and degradation. In this symposium, recent progress on the new mechanisms and adaptor molecules regarding regulation of RTK endocytosis will be introduced by researchers from five leading laboratories in this field. [J Physiol Sci. 2006;56 Suppl:S8]
