Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites
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Carrier Proteins / metabolism*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Female
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Humans
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Intracellular Signaling Peptides and Proteins*
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Membrane Proteins*
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Myristoylated Alanine-Rich C Kinase Substrate
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Phosphorylation
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Protein Binding
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Proteins / metabolism*
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Receptor, ErbB-2 / metabolism*
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Signal Transduction
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Substrate Specificity
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
Substances
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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MARCKS protein, human
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Membrane Proteins
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Proteins
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TOB1 protein, human
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Tumor Suppressor Proteins
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Myristoylated Alanine-Rich C Kinase Substrate
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Receptor, ErbB-2
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Cyclic AMP-Dependent Protein Kinases
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Tetradecanoylphorbol Acetate