P21-activated protein kinase (PAK2)-mediated c-jun phosphorylation at 5 threonine sites promotes cell transformation

Tingting Li, Jishuai Zhang, Feng Zhu, Weihong Wen, Tatiana Zykova, Xiang Li, Kangdong Liu, Cong Peng, Wei-Ya Ma, Guozheng Shi, Ziming Dong, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


The oncoprotein c-Jun is one of the components of the activator protein-1 (AP-1) transcription factor complex. AP-1 regulates the expression of many genes and is involved in a variety of biological functions such as cell transformation, proliferation, differentiation and apoptosis. AP-1 activates a variety of tumor-related genes and therefore promotes tumorigenesis and malignant transformation. Here, we found that epidermal growth factor (EGF) induces phosphorylation of c-Jun by P21-activated kinase (PAK) 2. Our data showed that PAK2 binds and phosphorylates c-Jun at five threonine sites (Thr2, Thr8, Thr89, Thr93 and Thr286) in vitro and ex vivo. 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. Mutation at all five c-Jun threonine sites phosphorylated by PAK2 decreased the transforming ability of JB6 cells. Knockdown of PAK2 in SK-MEL-5 melanoma cells also decreased colony formation, proliferation and AP-1 activity. These results indicated that PAK2/c-Jun signaling plays an important role in EGF-induced cell proliferation and transformation.

Original languageEnglish (US)
Pages (from-to)659-666
Number of pages8
Issue number5
StatePublished - May 2011


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