title: Identification of striated muscle activator of Rho signaling (STARS) as a novel calmodulin target by a newly developed genome-wide screen.
abstract: To search for novel target(s) of the Ca(2+)-signaling transducer, calmodulin (CaM), we performed a newly developed genome-wide CaM interaction screening of 19,676 GST-fused proteins expressed in human. We identified striated muscle activator of Rho signaling (STARS) as a novel CaM target and characterized its CaM binding ability and found that the Ca(2+)/CaM complex interacted stoichiometrically with the N-terminal region (Ala13-Gln35) of STARS in vitro as well as in living cells. Mutagenesis studies identified Ile20 and Trp33 as the essential hydrophobic residues in CaM anchoring. Furthermore, the CaM binding deficient mutant (Ile20Ala, Trp33Ala) of STARS further enhanced its stimulatory effect on SRF-dependent transcriptional activation. These results suggest a connection between Ca(2+)-signaling via excitation-contraction coupling and the regulation of STARS-mediated gene expression in muscles.
authors.affiliation: Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
authors.forename: Yusui
authors.initials: Y
authors.lastname: Furuya
authors.affiliation: CellFree Sciences Co., Ltd., Matsuyama, 790-8577, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Denda
authors.affiliation: Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Sakane
authors.affiliation: Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ogusu
authors.affiliation: Department of Biology, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Magari
authors.affiliation: Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanayama
authors.affiliation: CellFree Sciences Co., Ltd., Matsuyama, 790-8577, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Morishita
authors.affiliation: Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan. Electronic address: tokumit@okayama-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tokumitsu
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005820:Genetic Testing; D016678:Genome; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D051381:Rats; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
chemical_list: C464441:ABRA protein, human; D002147:Calmodulin; C489783:LHX2 protein, human; D060850:LIM-Homeodomain Proteins; D008840:Microfilament Proteins; D014157:Transcription Factors; D002118:Calcium
keywords: Ca(2+) signaling; Calmodulin; Genome-wide screening; Protein-protein interaction; STARS