Premium
Heregulin β1 induces the down regulation and the ubiquitin‐proteasome degradation pathway of p185 HER2 oncoprotein
Author(s) -
Magnifico A,
Tagliabue E,
Ardini E,
Casalini P,
Colnaghi M.I,
Ménard S
Publication year - 1998
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/s0014-5793(97)01612-8
Subject(s) - ubiquitin , proteasome , phosphorylation , neuregulin , tyrosine kinase , chemistry , endocytosis , kinase , microbiology and biotechnology , proteolysis , lactacystin , receptor , biochemistry , biology , proteasome inhibitor , enzyme , gene
Analysis of the fate of the p185 HER2 oncoprotein following activation by heregulin β1 revealed the induction of the tyrosine‐phosphorylation, down‐modulation, and polyubiquitination of p185 HER2 . Receptor ubiquitination was suppressed in cells treated with heregulin β1 in the presence of sodium azide, an inhibitor of ATP‐dependent reactions, or genistein, a tyrosine kinase protein inhibitor, indicating the requirement for kinase activity and ATP in p185 HER2 polyubiquitination. Ubiquitinated p185 HER2 was degradated by the 26S proteasome proteolytic pathway. Kinetics and inhibition experiments indicated that endocytosis of the receptor occurs downstream of the initiation of the degradation process.