title: Caveolin-3 undergoes SUMOylation by the SUMO E3 ligase PIASy: sumoylation affects G-protein-coupled receptor desensitization.
abstract: Caveolin (Cav) proteins in the plasma membrane have numerous binding partners, but the determinants of these interactions are poorly understood. We show here that Cav-3 has a small ubiquitin-like modifier (SUMO) consensus motif (ΨKX(D/E, where Ψ is a hydrophobic residue)) near the scaffolding domain and that Cav-3 is SUMOylated in a manner that is enhanced by the SUMO E3 ligase PIASy (protein inhibitor of activated STAT-y). Site-directed mutagenesis revealed that the consensus site lysine is the preferred SUMOylation site but that mutation of all lysines is required to abolish SUMOylation. Co-expression of a SUMOylation-deficient mutant of Cav-3 with β-adrenergic receptors (βARs) alters the expression level of β(2)ARs but not β(1)ARs following agonist stimulation, thus implicating Cav-3 SUMOylation in the mechanisms for β(2)AR but not β(1)AR desensitization. Expression of endothelial nitric-oxide synthase (NOS3) was not altered by the SUMOylation-deficient mutant. Thus, SUMOylation is a covalent modification of caveolins that influence the regulation of certain signaling partners.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla, California 92093, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Fuhs
authors.forename: Paul A
authors.initials: PA
authors.lastname: Insel
mesh_terms: D051244:Caveolin 3 / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008239:Lysine; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C417736:CAV3 protein, human; D051244:Caveolin 3; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D025841:Small Ubiquitin-Related Modifier Proteins; D044767:Ubiquitin-Protein Ligases; D008239:Lysine