Abstract 5153: PAK2-mediated c-Jun phosphorylation at 5 threonine sites promotes cell transformation

PAK2 plays an important role in cell proliferation, but the direct downstream proteins and precise regulatory mechanism involved in mediating PAK2’s role in proliferation are not yet clear. Here, we found that epidermal growth factor (EGF) induces phosphorylation of c-Jun by P21-activated kinase (PAK2). Knockdown of PAK2 in JB6 Cl41 (P+) cells had no effect on c-Jun phosphorylation at Ser63 or Ser73 but resulted in decreases in EGF-induced anchorage-independent cell transformation, proliferation and AP-1 activity. The oncoprotein c-Jun is one of the components of the activator protein-1 (AP-1) transcription factor complex. AP-1 activates a variety of tumor-related genes and promotes tumorigenesis and malignant transformation. Knockdown of PAK2 in SK-MEL-5 melanoma cells also decreased colony formation, proliferation and AP-1 activity. We found that PAK2 binds and phosphorylates c-Jun at five threonine sides (Thr2, Thr8, Thr89, Thr93 and Thr286) in vitro and in vivo. Mutation at all five sites decreased the transforming ability of JB6 cells. These results indicated that PAK2/c-Jun signaling plays an important role in tumorigenesis and provides an increased understanding of the signaling transduction mechanism of skin tumor cells and suggests that PAK2 might be a new chemopreventive or chemotherapeutic target. Citation Format: Tingting Li, Jishuai Zhang, Feng Zhu, Weihong Wen, Tatyana Zykova, Xiang Li, Kangdong Liu, Cong Peng, Wei-Ya Ma, Zigang Dong, Ann M. Bode. PAK2-mediated c-Jun phosphorylation at 5 threonine sites promotes cell transformation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5153. doi:10.1158/1538-7445.AM2013-5153