Critical involvement of RQCD1 in the EGFR-Akt pathway in mammary carcinogenesis.
We previously reported an important role of RQCD1 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 RQCD1 in regulation of the Akt activity as the downstream signal of epidermal growth factor receptor (EGFR). Knockdown of RQCD1 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 RQCD1. We subsequently defined that a region corresponding to 620-665th amino acids of GIGYF1 and 667-712th amino acids of GIGYF2 interacted with RQCD1. Furthermore, we found that RQCD1 was required for enhancement of the interaction of Grb10 with GIGYF1 and GIGYF2. Our findings in this study imply the functional mechanism of RQCD1 in the Akt activity regulation as a mediator in the EGFR-signaling pathway.
Ajiro
Masahiko
M
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Nishidate
Toshihiko
T
Katagiri
Toyomasa
T
Nakamura
Yusuke
Y
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D051383:GRB10 Adaptor Protein / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
C468527:CNOT9 protein, human; D002352:Carrier Proteins; C478015:GIGYF1 protein, human; C478016:GIGYF2 protein, human; C096358:GRB10 protein, human; D014157:Transcription Factors; D051383:GRB10 Adaptor Protein; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt