Open AccessThe interaction of p130Cas with PKN 3 promotes malignant growth
Author(s) -
Gemperle Jakub,
Dibus Michal,
Koudelková Lenka,
Rosel Daniel,
Brábek Jan
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12401
Subject(s) - proto oncogene tyrosine protein kinase src , sh3 domain , signal transducing adaptor protein , microbiology and biotechnology , biology , tyrosine kinase , cancer research , kinase , phosphorylation , signal transduction
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 PKN 3, which is implicated in prostate and breast cancer growth downstream of phosphoinositide 3‐kinase. This direct interaction is mediated by the p130Cas SH 3 domain and the centrally located PKN 3 polyproline sequence. PKN 3 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 PKN 3–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 PKN 3–p130Cas complex represents an attractive therapeutic target in late‐stage malignancies.