Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine kinases

FEBS Letters

Waterman, Hadassa¹  Yarden, Yosef¹ 

[1] Department of Biological Regulation, the Weizmann Institute of Science, Rehovot 76100, Israel

关键词: Clathrin;    Growth factor;    Oncogene;    Review;    Signal transduction;    Tyrosine kinase;    Ubiquitin;   

DOI  :  10.1016/S0014-5793(01)02117-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The major process that regulates the amplitude and kinetics of signal transduction by tyrosine kinase receptors is endocytic removal of active ligand–receptor complexes from the cell surface, and their subsequent sorting to degradation or to recycling. Using the ErbB family of receptor tyrosine kinases we exemplify the diversity of the down regulation process, and concentrate on two sorting steps whose molecular details are emerging. These are the Eps15-mediated sorting to clathrin-coated regions of the plasma membrane and the c-Cbl-mediated targeting of receptors to lysosomal degradation. Like in yeast cells, sorting involves not only protein phosphorylation but also conjugation of ubiquitin molecules. The involvement of other molecules is reviewed and recent observations that challenge the negative regulatory role of endocytosis are described. Finally, we discuss the relevance of receptor down regulation to cancer therapy.

【 授权许可】

Unknown