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Direct binding of Copine3 with Jab1 activates downstream ErbB2 signaling and motility in SKBr3 breast cancer cells

  • Authors:
    • Hye Young Choi
    • Nammi Park
    • Jae Boem Na
    • Eun Sook Ko
    • Jae-Yong Park
    • Jae Cheal Yoo

  • View Affiliations

  • Published online on: December 2, 2015     https://doi.org/10.3892/or.2015.4472
  • Pages: 1147-1152
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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.
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February-2016
Volume 35 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Choi HY, Park N, Na JB, Ko ES, Park J and Yoo JC: Direct binding of Copine3 with Jab1 activates downstream ErbB2 signaling and motility in SKBr3 breast cancer cells. Oncol Rep 35: 1147-1152, 2016.
APA
Choi, H.Y., Park, N., Na, J.B., Ko, E.S., Park, J., & Yoo, J.C. (2016). Direct binding of Copine3 with Jab1 activates downstream ErbB2 signaling and motility in SKBr3 breast cancer cells. Oncology Reports, 35, 1147-1152. https://doi.org/10.3892/or.2015.4472
MLA
Choi, H. Y., Park, N., Na, J. B., Ko, E. S., Park, J., Yoo, J. C."Direct binding of Copine3 with Jab1 activates downstream ErbB2 signaling and motility in SKBr3 breast cancer cells". Oncology Reports 35.2 (2016): 1147-1152.
Chicago
Choi, H. Y., Park, N., Na, J. B., Ko, E. S., Park, J., Yoo, J. C."Direct binding of Copine3 with Jab1 activates downstream ErbB2 signaling and motility in SKBr3 breast cancer cells". Oncology Reports 35, no. 2 (2016): 1147-1152. https://doi.org/10.3892/or.2015.4472