title: Four-and-a-half LIM Domains 1 (FHL1) Protein Interacts with the Rho Guanine Nucleotide Exchange Factor PLEKHG2/FLJ00018 and Regulates Cell Morphogenesis.
abstract: PLEKHG2/FLJ00018 is a Gβγ-dependent guanine nucleotide exchange factor for the small GTPases Rac and Cdc42 and has been shown to mediate the signaling pathways leading to actin cytoskeleton reorganization. Here we showed that the zinc finger domain-containing protein four-and-a-half LIM domains 1 (FHL1) acts as a novel interaction partner of PLEKHG2 by the yeast two-hybrid system. Among the isoforms of FHL1 (i.e. FHL1A, FHL1B, and FHL1C), FHL1A and FHL1B interacted with PLEKHG2. We found that there was an FHL1-binding region at amino acids 58-150 of PLEKHG2. The overexpression of FHL1A but not FHL1B enhanced the PLEKHG2-induced serum response element-dependent gene transcription. The co-expression of FHL1A and Gβγ synergistically enhanced the PLEKHG2-induced serum response element-dependent gene transcription. Increased transcription activity was decreased by FHL1A knock-out with the CRISPR/Cas9 system. Compared with PLEKHG2-expressing cells, the number and length of finger-like protrusions were increased in PLEKHG2-, Gβγ-, and FHL1A-expressing cells. Our results provide evidence that FHL1A interacts with PLEKHG2 and regulates cell morphological change through the activity of PLEKHG2.
authors.affiliation: From the United Graduate School of Drug Discovery and Medical Information Sciences and.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Sato
authors.affiliation: the Department of Molecular Pathobiochemistry, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1193, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kimura
authors.affiliation: From the United Graduate School of Drug Discovery and Medical Information Sciences and.
authors.forename: Kazue
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: From the United Graduate School of Drug Discovery and Medical Information Sciences and.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: the Department of Molecular Pathobiochemistry, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1193, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Okano
authors.affiliation: the Department of Molecular Pathobiochemistry, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1193, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagaoka
authors.affiliation: the Kazusa DNA Research Institute, 2-6-7 Kazusa-kamatari, Kisarazu, Chiba 292-0818, Japan, and.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagase
authors.affiliation: From the United Graduate School of Drug Discovery and Medical Information Sciences and.|the Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kitade
authors.affiliation: From the United Graduate School of Drug Discovery and Medical Information Sciences and hueda@gifu-u.ac.jp.|the Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
mesh_terms: D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D027602:Serum Response Element / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: C101149:FHL1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; C527535:PLEKHG2 protein, human; D020033:Protein Isoforms
keywords: G protein; Rho (Rho GTPase); guanine nucleotide exchange factor (GEF); protein-protein interaction; yeast two-hybrid