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The muscle‐specific transcription cofactor Vgll2 promotes myogenic differentiation through a casein kinase II dependent mechanism
Author(s) -
Teng Allen CT,
Belanger Melanie I,
Stewart Alexandre FR
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.782.18
Subject(s) - phosphorylation , biology , transcription factor , casein kinase 2 , serine , microbiology and biotechnology , mutant , protein kinase a , biochemistry , gene , cyclin dependent kinase 2
In D. melanogaster , the transcription factor of Scalloped (Sd) and its cofactor, Vestigial (Vg), control the development of indirect flight muscles and wings. Vestigial‐like 2 (Vgll2), a vertebrates homolog of Vg, is specifically expressed in skeletal muscle. Over‐expression of Vgll2 enhances myotube formation whereas Vgll2 knockdown blocks myogenic differentiation, demonstrating the important role of Vgll2 in skeletal muscle differentiation. However, the mechanisms that regulate Vgll2 interaction with TEA domain (TEAD) transcription factors (homologs of Sd) and MEF2 remain poorly characterized. An evolutionarily conserved casein kinase II (CKII) phosphorylation site (Serine 96) in all vestigial‐like (Vgll) proteins. Bacterially‐expressed purified GST‐Vgll2 protein was selectively phosphorylated by CKII in vitro. Two mutant constructs generated by site‐directed mutagenesis, S96A and S96E, were tested in mammalian‐two hybrid assays. The alanine mutant completely abolished the Vgll2‐TEAD1 interaction whereas the glutamate mutant enhanced this interaction. Immunocytochemistry showed that the alanine mutant was inappropriately localized in the periphery of the nucleus while the glutamate mutant was associated with euchromatin. These results imply that phosphorylation of the serine 96 residue is necessary for the Vgll2‐based myogenic differentiation.