Heregulin β1 induces the down regulation and the ubiquitin‐proteasome degradation pathway of p185HER2 oncoprotein

FEBS Letters

Ardini, E¹  Casalini, P¹  Ménard, S¹  Magnifico, A¹  Tagliabue, E¹  Colnaghi, M.I¹ 

[1] Division of Experimental Oncology E, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy

关键词: p185HER2 oncoprotein;    Down-modulation;    Ubiquitination;    Proteasome enzyme;    EGF;    epidermal growth factor;    NDF;    neu differentiation factor;    KLH;    keyhole-limpet hemocyanin;    PDGF;    platelet-derived growth factor;    TCR;    T cell receptor;    MHC;    major histocompatibility complex;   

DOI  :  10.1016/S0014-5793(97)01612-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown