The interaction of p130Cas with PKN3 promotes malignant growth
Protein p130Cas constitutes an adaptor protein mainly involved in integrin signaling downstream of Src kinase. Owing to its modular structure, p130Cas acts as a general regulator of cancer cell growth and invasiveness induced by different oncogenes. However, other mechanisms of p130Cas signaling lea...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-02-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12401 |
| _version_ | 1818293841292165120 |
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| author | Jakub Gemperle Michal Dibus Lenka Koudelková Daniel Rosel Jan Brábek |
| author_facet | Jakub Gemperle Michal Dibus Lenka Koudelková Daniel Rosel Jan Brábek |
| author_sort | Jakub Gemperle |
| collection | DOAJ |
| description | Protein p130Cas constitutes an adaptor protein mainly involved in integrin signaling downstream of Src kinase. Owing to its modular structure, p130Cas acts as a general regulator of cancer cell growth and invasiveness induced by different oncogenes. However, other mechanisms of p130Cas signaling leading to malignant progression are poorly understood. Here, we show a novel interaction of p130Cas with Ser/Thr kinase PKN3, which is implicated in prostate and breast cancer growth downstream of phosphoinositide 3‐kinase. This direct interaction is mediated by the p130Cas SH3 domain and the centrally located PKN3 polyproline sequence. PKN3 is the first identified Ser/Thr kinase to bind and phosphorylate p130Cas and to colocalize with p130Cas in cell structures that have a pro‐invasive function. Moreover, the PKN3–p130Cas interaction is important for mouse embryonic fibroblast growth and invasiveness independent of Src transformation, indicating a mechanism distinct from that previously characterized for p130Cas. Together, our results suggest that the PKN3–p130Cas complex represents an attractive therapeutic target in late‐stage malignancies. |
| first_indexed | 2024-12-13T03:22:16Z |
| format | Article |
| id | doaj.art-a8150fc97bc04d568eba1811cd1a86f5 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-13T03:22:16Z |
| publishDate | 2019-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-a8150fc97bc04d568eba1811cd1a86f52022-12-22T00:01:20ZengWileyMolecular Oncology1574-78911878-02612019-02-0113226428910.1002/1878-0261.12401The interaction of p130Cas with PKN3 promotes malignant growthJakub Gemperle0Michal Dibus1Lenka Koudelková2Daniel Rosel3Jan Brábek4Department of Cell Biology Faculty of Science – Biocev Charles University Prague 2 Czech RepublicDepartment of Cell Biology Faculty of Science – Biocev Charles University Prague 2 Czech RepublicDepartment of Cell Biology Faculty of Science – Biocev Charles University Prague 2 Czech RepublicDepartment of Cell Biology Faculty of Science – Biocev Charles University Prague 2 Czech RepublicDepartment of Cell Biology Faculty of Science – Biocev Charles University Prague 2 Czech RepublicProtein p130Cas constitutes an adaptor protein mainly involved in integrin signaling downstream of Src kinase. Owing to its modular structure, p130Cas acts as a general regulator of cancer cell growth and invasiveness induced by different oncogenes. However, other mechanisms of p130Cas signaling leading to malignant progression are poorly understood. Here, we show a novel interaction of p130Cas with Ser/Thr kinase PKN3, which is implicated in prostate and breast cancer growth downstream of phosphoinositide 3‐kinase. This direct interaction is mediated by the p130Cas SH3 domain and the centrally located PKN3 polyproline sequence. PKN3 is the first identified Ser/Thr kinase to bind and phosphorylate p130Cas and to colocalize with p130Cas in cell structures that have a pro‐invasive function. Moreover, the PKN3–p130Cas interaction is important for mouse embryonic fibroblast growth and invasiveness independent of Src transformation, indicating a mechanism distinct from that previously characterized for p130Cas. Together, our results suggest that the PKN3–p130Cas complex represents an attractive therapeutic target in late‐stage malignancies.https://doi.org/10.1002/1878-0261.12401BCAR1CASp130CasPKN3SH3Src |
| spellingShingle | Jakub Gemperle Michal Dibus Lenka Koudelková Daniel Rosel Jan Brábek The interaction of p130Cas with PKN3 promotes malignant growth Molecular Oncology BCAR1 CAS p130Cas PKN3 SH3 Src |
| title | The interaction of p130Cas with PKN3 promotes malignant growth |
| title_full | The interaction of p130Cas with PKN3 promotes malignant growth |
| title_fullStr | The interaction of p130Cas with PKN3 promotes malignant growth |
| title_full_unstemmed | The interaction of p130Cas with PKN3 promotes malignant growth |
| title_short | The interaction of p130Cas with PKN3 promotes malignant growth |
| title_sort | interaction of p130cas with pkn3 promotes malignant growth |
| topic | BCAR1 CAS p130Cas PKN3 SH3 Src |
| url | https://doi.org/10.1002/1878-0261.12401 |
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