Mitogenesis and endocytosis: What's at the INTERSECTIoN?

Endocytosis is a regulated physiological process by which cell surface prot eins are internalized along with extracellular factors such as nutrients, p athogens, peptides, toxins, etc. The process begins with the invagination o f small regions of the plasma membrane which ultimately form intracellullar vesicles. These internalized vesicles may shuttle back to the plasma membr ane to recycle the membrane components or they may be targeted for degradat ion. One role for endocytosis is in the attenuation of receptor signaling. For example, desensitization of activated membrane bound receptors such as G-protein coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs) occ urs, in part, through endocytosis of the activated receptor. However, accum ulating evidence suggests that endocytosis also mediates intracellular sign aling. In this review, we discuss the experimental data that implicate endo cytosis as a critical component in cellular signal transduction, both in th e initiation of a signal as well as in the termination of a signal. Further more, we focus our attention on a recently described adaptor protein, inter sectin (ITSN), which provides a link to both the endocytic and the mitogeni c machinery of a cell. Thus, ITSN functions at a crossroad in the biochemic al regulation of cell function.