Critical involvement of RQCD1 in the EGFR-Akt pathway in mammary carcinogenesis.

We previously reported an important role of in mammary carcinogenesis through the interaction with Grb10 interacting GYF protein 1 (GIGYF1), Grb10 interacting GYF protein 2 (GIGYF2) and growth factor receptor binding protein 10 (Grb10). In this study, we investigated the biological mechanism of duanyu1745CD1 in regulation of the Akt activity as the downstream signal of epidermal growth factor receptor (EGFR). Knockdown of duanyu1745CD1 reduced the Akt phosphorylation level that was induced by epidermal growth factor (EGF) stimulation. We found a possible formation of the big complex involved in the Akt activity including Akt, EGFR, GIGYF1 and GIGYF2, Grb10 and We subsequently defined that a region corresponding to 620-665th amino acids of GIGYF1 and 667-712th amino acids of GIGYF2 interacted with duanyu1745CD1. Furthermore, we found that duanyu1745CD1 was required for enhancement of the interaction of Grb10 with GIGYF1 and GIGYF2. Our findings in this study imply the functional mechanism of duanyu1745CD1 in the Akt activity regulation as a mediator in the EGFR-signaling pathway.

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