Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation.
The biochemical path for the activation of ErbB-2 by PKC activator was investigated 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 through the binding with ErbB-2. The phosphorylation site domain ... (PSD) of MARCKS 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 cells in response to PMA treatment. The present study proposes that MARCKS phosphorylation by PKC removes Tob from ErbB-2 by increasing its binding affinity with Tob, and thereby activates the ErbB-2 mediated signal transduction.
Mesh Terms:
Binding Sites, Carrier Proteins, Cyclic AMP-Dependent Protein Kinases, Female, Humans, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Phosphorylation, Protein Binding, Proteins, Receptor, erbB-2, Signal Transduction, Substrate Specificity, Tetradecanoylphorbol Acetate, Tumor Cells, Cultured, Tumor Suppressor Proteins
Binding Sites, Carrier Proteins, Cyclic AMP-Dependent Protein Kinases, Female, Humans, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Phosphorylation, Protein Binding, Proteins, Receptor, erbB-2, Signal Transduction, Substrate Specificity, Tetradecanoylphorbol Acetate, Tumor Cells, Cultured, Tumor Suppressor Proteins
Biochem. Biophys. Res. Commun.
Date: May. 04, 2001
PubMed ID: 11327693
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