Effects of CSK Homologous Kinase Overexpression on HER2/Neu-Mediated Signal Transduction Pathways in Breast Cancer Cells
Abstract
Our proposal aims to investigate in details the potential function of CHK in breast cancer as a signal transducer in the signaling pathway from HER2/Neu receptor. The studies conducted in the period reported included: 1) the assessment of the effects of CHK on the main signaling pathways (RAFTK-and Akt-mediated) induced by the activation of HER2/Neu receptor, 2) comparison of the effects in vitro of wild-type CHK and mutant forms (enhanced/abolished binding to HER2/Neu receptor) of this CHK on the heregulin-induced activation of Src-family kinases. Our major findings are as follows: la) CHK directly associates with RAFTK kinase and is a negative regulator of RAFTK activation in HER2/Neu elicited transduction pathway; lb) CHK under some circumstances facilitates activation of Akt following activation of HER2/Neu receptor; 2) the effects of CHK on Src kinase activation are directly coupled with the ability of CHK to bind the activated form of HER2/Neu receptor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA416967
Entities
People
- Hava Avraham
- Radoslaw Zagozdzon
Organizations
- Beth Israel Deaconess Medical Center