Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation

The biochemical path for the activation of ErbB-2 by PKC activator was inve stigated in MDA-MB-231 human breast cancer cells. We found that PMA-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) increased its binding with Tob that exerts an anti-proliferative effect thr ough the binding with ErbB-2. The phosphorylation site domain (PSD) of MARC KS was relevant to its interaction with Tob. Decreased binding of Tob with ErbB-2 and subsequent activation of ErbB-2 were observed in MDA-MB-231 cell s in response to PMA treatment. The present study proposes that MARCKS phos phorylation by PKC removes Tob from ErbB-2 by increasing its binding affini ty with Tob, and thereby activates the ErbB-2 mediated signal transduction. (C) 2001 Academic Press.