« Previous AbstractEstimation of Knudsen diffusion coefficients from tracer experiments conducted with a binary gas system and a porous medium    Next AbstractEnantioselective sensing of insect pheromones in water »

J Cell Biol

Title:		Cytoplasmic tail phosphorylation of the alpha-factor receptor is required for its ubiquitination and internalization
Author(s):		Hicke L; Zanolari B; Riezman H;
Address:		"Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA. 1-hicke@nwu.edu"
Journal Title:		J Cell Biol
Year:		1998
Volume:		141
Issue:		2
Page Number:		349 - 358
DOI:		10.1083/jcb.141.2.349
ISSN/ISBN:		0021-9525 (Print) 1540-8140 (Electronic) 0021-9525 (Linking)
Abstract:		"G protein-coupled (GPC) receptors are phosphorylated in response to ligand binding, a modification that promotes receptor desensitization or downregulation. The alpha-factor pheromone receptor (Ste2p) of Saccharomyces cerevisiae is a GPC receptor that is hyperphosphorylated and ubiquitinated upon binding alpha-factor. Ubiquitination triggers Ste2p internalization into the endocytic pathway. Here we demonstrate that phosphorylation of Ste2p promotes downregulation by positively regulating ubiquitination and internalization. Serines and a lysine are essential elements of the Ste2p SINNDAKSS internalization signal that can mediate both constitutive and ligand-stimulated endocytosis. The SINNDAKSS serines are required for receptor phosphorylation which, in turn, facilitates ubiquitination of the neighboring lysine. Constitutive phosphorylation is required to promote constitutive internalization, and is also a prerequisite for ligand-induced phosphorylation at or near the SINNDAKSS sequence. Mutants defective in yeast casein kinase I homologues are unable to internalize alpha-factor, and do not phosphorylate or ubiquitinate the receptor, indicating that these kinases play a direct or indirect role in phosphorylating the receptor. Finally, we provide evidence that the primary function of phosphorylation controlled by the SINNDAKSS sequence is to trigger receptor internalization, demonstrating that phosphorylation-dependent endocytosis is an important mechanism for the downregulation of GPC receptor activity"
Keywords:		"Amino Acid Sequence Casein Kinases Cytoplasm/*metabolism Endocytosis/*physiology Lysine/metabolism Mating Factor Molecular Sequence Data Mutation Peptides/metabolism/pharmacology Phosphorylation Protein Kinases/genetics/physiology Receptors, Mating Factor;"
Notes:		"MedlineHicke, L Zanolari, B Riezman, H eng 1 R01 DK53257-01/DK/NIDDK NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 1998/05/23 J Cell Biol. 1998 Apr 20; 141(2):349-58. doi: 10.1083/jcb.141.2.349"