P21-activated Protein Kinase (PAK2)-mediated C-Jun Phosphorylation at 5 Threonine Sites Promotes Cell Transformation

Overview

Journal Carcinogenesis

Specialty Oncology

Date 2010 Dec 24

PMID 21177766

Citations 15

Authors

Tingting Li

Jishuai Zhang

Feng Zhu

Weihong Wen

Tatyana Zykova

Xiang Li

Kangdong Liu

Cong Peng

Weiya Ma

Guozheng Shi

Ziming Dong

Ann M Bode

Zigang Dong

Affiliations

Soon will be listed here.

Abstract

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.

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