title: Direct binding of Copine3 with Jab1 activates downstream ErbB2 signaling and motility in SKBr3 breast cancer cells.
abstract: Copine3, a known calcium-dependent membrane binding protein, contains two tandem C2 domains and an A domain. This protein has been shown to interact with receptor tyrosine kinase 2 (ErbB2), but little is known concerning the physiological function of Copine3. To better understand its cellular function, we carried out a yeast two-hybrid screen to find Copine3 binding partners. Among the identified proteins, Jun activation domain-binding protein 1 (Jab1) appears to directly interact with Copine3. This physical interaction between Copine3 and Jab1 as well as the specific binding regions of both proteins were confirmed in vitro and in vivo. Our results also demonstrate that binding of Copine3 to ErbB2 is increased when Jab1 is overexpressed in SKBr3 breast cancer cells. Furthermore, two ErbB2 downstream signaling proteins [phosphatidylinositol 3 (PI3) kinase and protein kinase B (AKT)] were also activated by Jab1 overexpression in these cells. These data suggest that binding of Copine3 and Jab1 regulates, at least to some extent, the ErbB2 signaling pathway. Moreover, overexpression of both Copine3 and Jab1 in SKBr3 cells effectively increased cellular migration. Collectively, our findings indicating that Jab1 enhances the ErbB2 binding ability of Copine3, further activating the ErbB2 signaling pathways involved in breast cancer cell pathogenesis.
authors.affiliation: Department of Radiology, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Lab of Aquatic Animal Diseases, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Nammi
authors.initials: N
authors.lastname: Park
authors.affiliation: Department of Radiology, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea.
authors.forename: Jae Boem
authors.initials: JB
authors.lastname: Na
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Ko
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 136-703, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 136-703, Republic of Korea.
authors.forename: Jae Cheal
authors.initials: JC
authors.lastname: Yoo
mesh_terms: D000818:Animals; D001665:Binding Sites; D001943:Breast Neoplasms / Q000473:pathology*; D000075686:COP9 Signalosome Complex; D019556:COS Cells; D045744:Cell Line, Tumor; D002465:Cell Movement; D002522:Chlorocebus aethiops; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014161:Transduction, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D000075686:COP9 Signalosome Complex; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D010447:Peptide Hydrolases; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; C415882:copine III; C508053:ERBB2 protein, human; C494918:AKT1 protein, human; C501488:COPS5 protein, human