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Regulation of Receptor Tyrosine Kinase Signaling by Endocytic Trafficking
Author(s) -
Wiley H. Steven,
Burke Patrick M.
Publication year - 2001
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1034/j.1600-0854.2001.020103.x
Subject(s) - biology , endocytic cycle , microbiology and biotechnology , receptor tyrosine kinase , tyrosine kinase , signal transduction , ror1 , endocytosis , receptor , platelet derived growth factor receptor , genetics , growth factor
Activated receptor tyrosine kinase (RTK) receptors are rapidly internalized and eventually delivered to the lysosomes. Although ligand‐induced endocytosis was originally thought to be a mechanism of receptor inactivation, many studies suggest that receptors remain active within endosomes. This review discusses the role that internalized signaling complexes may play in different RTK systems including recent data on how ubiquitination may regulate this process. In general, it appears that some receptor systems have evolved to enhance endosomal signaling, as is the case for TrkA and NGF. In contrast, the insulin receptor system appears to limit the extent of endosomal signaling. The EGFR system is the intermediate example. In this case, some signals are specifically generated from the cell surface while others appear to be generated from within endosomes. This may act as a mechanism to produce ligand‐specific signals. Thus, trafficking could play diverse roles in receptor signaling, depending on the specific cell and tissue type.