Myristoylated alanine-rich C kinase substrate (MARCKS) is a substrate for protein kinase C (PKC). When human breast cancer cells were treated with phorbol 12-myristate 13-acetate (PMA), the activator of PKC, the phosphorylation of MARCKS and its binding with Tob were increased, but the binding of Tob with ErbB-2 was decreased. These results propose that MARCKS phosphorylation by PKC activation dissociates Tob from ErbB-2, and the signaling pathway through ErbB-2 is activated. Focal adhesion kinase (FAK) is a non-receptor, non-membrane tyrosine kinase and is involved in integrin-mediated Erk2/MAP kinase activation and its phosphorylation is increased when PKC is active. In attempt to examine the activation mechanism of FAK, we test a hypothesis that activity of FAK is mediated by Tob. However, FAK did not bind with Tob, suggesting that another mechanism mat exist and Tob is not involved in the activation of FAK-mediated signaling pathway by PKC activation.
