The GTPase Regulatory Proteins Pix and Git Control Tissue Growth via the Hippo Pathway
| Autor: | Marla Tipping, Carole L.C. Poon, Lucas G. Dent, Kieran F. Harvey, Xiaomeng Zhang, Joffrey L. Degoutin, Alexey Veraksa |
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| Rok vydání: | 2015 |
| Předmět: |
Male
endocrine system animal structures Regulator Growth GTPase Protein Serine-Threonine Kinases Biology Article General Biochemistry Genetics and Molecular Biology GTP-Binding Protein Regulators Animals Drosophila Proteins Hippo signaling pathway Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) Kinase Cadherin GTPase-Activating Proteins fungi Autophosphorylation Intracellular Signaling Peptides and Proteins body regions Drosophila melanogaster Biochemistry Hippo signaling Female sense organs Guanine nucleotide exchange factor General Agricultural and Biological Sciences Dimerization Rho Guanine Nucleotide Exchange Factors Signal Transduction |
| Zdroj: | Current Biology. 25:124-130 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2014.11.041 |
| Popis: | Summary The Salvador-Warts-Hippo (Hippo) pathway is a conserved regulator of organ size and is deregulated in human cancers [1]. In epithelial tissues, the Hippo pathway is regulated by fundamental cell biological properties, such as polarity and adhesion, and coordinates these with tissue growth [2–4]. Despite its importance in disease, development, and regeneration, the complete set of proteins that regulate Hippo signaling remain undefined. To address this, we used proteomics to identify proteins that bind to the Hippo (Hpo) kinase. Prominent among these were PAK-interacting exchange factor (known as Pix or RtGEF) and G-protein-coupled receptor kinase-interacting protein (Git). Pix is a conserved Rho-type guanine nucleotide exchange factor (Rho-GEF) homologous to Beta-PIX and Alpha-PIX in mammals. Git is the single Drosophila melanogaster homolog of the mammalian GIT1 and GIT2 proteins, which were originally identified in the search for molecules that interact with G-protein-coupled receptor kinases [5]. Pix and Git form an oligomeric scaffold to facilitate sterile 20-like kinase activation and have also been linked to GTPase regulation [5–8]. We show that Pix and Git regulate Hippo-pathway-dependent tissue growth in D. melanogaster and that they do this in parallel to the known upstream regulator Fat cadherin. Pix and Git influence activity of the Hpo kinase by acting as a scaffold complex, rather than enzymes, and promote Hpo dimerization and autophosphorylation of Hpo's activation loop. Therefore, we provide important new insights into an ancient signaling network that controls the growth of metazoan tissues. |
| Databáze: | OpenAIRE |
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