Specific α-arrestins negatively regulate Saccharomyces cerevisiae pheromone response by down-modulating the G-protein-coupled receptor Ste2
| Autor: | Alvaro, Christopher G, O'Donnell, Allyson F, Prosser, Derek C, Augustine, Andrew A, Goldman, Aaron, Brodsky, Jeffrey L, Cyert, Martha S, Wendland, Beverly, Thorner, Jeremy |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Endosomal Sorting Complexes Required for Transport Arrestins Calcineurin 1.1 Normal biological development and functioning Cell Cycle Ubiquitination Ubiquitin-Protein Ligase Complexes Membrane Proteins Saccharomyces cerevisiae Biological Sciences Medical and Health Sciences Pheromones Fungal Gene Expression Regulation Underpinning research Receptors Generic health relevance Phosphorylation Peptides Carrier Proteins Mating Factor Signal Transduction Developmental Biology |
| Zdroj: | Alvaro, CG; O'Donnell, AF; Prosser, DC; Augustine, AA; Goldman, A; Brodsky, JL; et al.(2014). Specific α-arrestins negatively regulate Saccharomyces cerevisiae pheromone response by down-modulating the G-protein-coupled receptor Ste2. Molecular and Cellular Biology, 34(14), 2660-2681. doi: 10.1128/MCB.00230-14. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/5cj6p3gp Molecular and cellular biology, vol 34, iss 14 |
| DOI: | 10.1128/MCB.00230-14. |
| Popis: | G-protein-coupled receptors (GPCRs) are integral membrane proteins that initiate responses to extracellular stimuli by mediating ligand-dependent activation of cognate heterotrimeric G proteins. In yeast, occupancy of GPCR Ste2 by peptide pheromone α-factor initiates signaling by releasing a stimulatory Gβγ complex (Ste4-Ste18) from its inhibitory Gα subunit (Gpa1). Prolonged pathway stimulation is detrimental, and feedback mechanisms have evolved that act at the receptor level to limit the duration of signaling and stimulate recovery from pheromone-induced G1arrest, including upregulation of the expression of an α-factor-degrading protease (Bar1), a regulator of G-protein signaling protein (Sst2) that stimulates Gpa1-GTP hydrolysis, and Gpa1 itself. Ste2 is also downregulated by endocytosis, both constitutive and ligand induced. Ste2 internalization requires its phosphorylation and subsequent ubiquitinylation by membrane-localized protein kinases (Yck1 and Yck2) and a ubiquitin ligase (Rsp5). Here, we demonstrate that three different members of the α-arrestin family (Ldb19/Art1, Rod1/Art4, and Rog3/Art7) contribute to Ste2 desensitization and internalization, and they do so by discrete mechanisms. We provide genetic and biochemical evidence that Ldb19 and Rod1 recruit Rsp5 to Ste2 via PPXY motifs in their C-terminal regions; in contrast, the arrestin fold domain at the N terminus of Rog3 is sufficient to promote adaptation. Finally, we show that Rod1 function requires calcineurin-dependent dephosphorylation. © 2014, American Society for Microbiology. |
| Databáze: | OpenAIRE |
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