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.

• MeSH
• fibroblasty metabolismus   MeSH
• fosforylace MeSH
• fosfothreonin metabolismus   MeSH
• invazivní růst nádoru MeSH
• kontraktilní svazky metabolismus   MeSH
• lidé MeSH
• myši nahé MeSH
• nádory metabolismus   patologie   MeSH
• podozomy metabolismus   MeSH
• pohyb buněk MeSH
• proliferace buněk MeSH
• proteinkinasa C metabolismus   MeSH
• pseudopodia metabolismus   MeSH
• skupina kinas odvozených od src-genu metabolismus   MeSH
• substrátový protein asociovaný s Crk metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH