1. Academic Validation
  2. Phosphorylation of moesin by Jun N-terminal kinase is important for podosome rosette formation in Src-transformed fibroblasts

Phosphorylation of moesin by Jun N-terminal kinase is important for podosome rosette formation in Src-transformed fibroblasts

  • J Cell Sci. 2013 Dec 15;126(Pt 24):5670-80. doi: 10.1242/jcs.134361.
Yi-Ru Pan 1 Wei-Shan Tseng Po-Wei Chang Hong-Chen Chen
Affiliations

Affiliation

  • 1 Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan.
Abstract

Podosomes are actin-based membrane protrusions that facilitate extracellular matrix degradation and motility of invasive cells. Podosomes can self-organize into large rosette-like structures in Src-transformed fibroblasts, osteoclasts and some highly invasive Cancer cells. However, the mechanism of this assembly remains obscure. In this study, we show that the suppression of Jun N-terminal kinase (JNK) by the JNK Inhibitor SP600125 or short-hairpin RNA inhibited podosome rosette formation in SrcY527F-transformed NIH3T3 fibroblasts. In addition, SrcY527F was less able to induce podosome rosettes in JNK1-null or JNK2-null mouse embryo fibroblasts than in wild-type counterparts. The kinase activity of JNK was essential for promoting podosome rosette formation but not for its localization to podosome rosettes. Moesin, a member of the ERM (ezrin, radixin and moesin) protein family, was identified as a substrate of JNK. We show that the phosphorylation of moesin at Thr558 by JNK was important for podosome rosette formation in SrcY527F-transformed NIH3T3 fibroblasts. Taken together, our results unveil a novel role of JNK in podosome rosette formation through the phosphorylation of moesin.

Keywords

ERM; JNK; Moesin; Phosphorylation; Podosome rosettes.

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