title: Phosphorylation of moesin by Jun N-terminal kinase is important for podosome rosette formation in Src-transformed fibroblasts.
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.
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Yi-Ru
authors.initials: YR
authors.lastname: Pan
authors.forename: Wei-Shan
authors.initials: WS
authors.lastname: Tseng
authors.forename: Po-Wei
authors.initials: PW
authors.lastname: Chang
authors.forename: Hong-Chen
authors.initials: HC
authors.lastname: Chen
mesh_terms: D000818:Animals; D021961:Cell Membrane Structures / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology* / Q000648:ultrastructure; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D041681:NIH 3T3 Cells; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins; C496061:PXN protein, human; D051419:Paxillin; C071058:moesin; D048056:Mitogen-Activated Protein Kinase 9; D019061:src-Family Kinases; D048055:Mitogen-Activated Protein Kinase 8
keywords: ERM; JNK; Moesin; Phosphorylation; Podosome rosettes