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CSF‐1 and TPA stimulate independent pathways leading to lysosomal degradation or regulated intramembrane proteolysis of the CSF‐1 receptor
Author(s) -
Glenn Gary,
van der Geer Peter
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.10.031
Subject(s) - downregulation and upregulation , proteolysis , receptor , microbiology and biotechnology , chemistry , signal transduction , inducer , macrophage colony stimulating factor , receptor tyrosine kinase , tyrosine kinase , ubiquitin , biology , biochemistry , macrophage , enzyme , gene , in vitro
The CSF‐1 receptor is a protein‐tyrosine kinase that has been shown to undergo regulated intramembrane proteolysis, or RIPping. Here, we have compared receptor downregulation and RIPping in response to CSF‐1 and TPA. Our studies show that CSF‐1 is a relatively poor inducer of RIPping and that CSF‐1‐induced receptor downregulation is largely independent of RIPping. TPA is a strong inducer of RIPping and TPA‐induced receptor downregulation is mediated by RIPping. We further found that RIPping is dependent on TACE or a TACE‐like protease, that CSF‐1 and TPA use independent pathways to initiate RIPping, and that the intracellular domain is targeted for degradation through ubiquitination.