Cluster of differentiation antigen 4 (CD4) endocytosis and adaptor complex binding require activation of the CD4 endocytosis signal by serine phosphorylation.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Cluster of differentiation antigen 4 (CD4) endocytosis and adaptor complex binding require activation of the CD4 endocytosis signal by serine phosphorylation.

Mol Biol Cell. 1999 Mar;10(3):677-91. Unique Identifier : AIDSLINE MED/99169014
Pitcher C; Honing S; Fingerhut A; Bowers K; Marsh M; Medical Research Council Laboratory for Molecular Cell Biology; and Department of Biochemistry, University College London, London; WC1E 6BT, United Kingdom.

Abstract: Cluster of differentiation antigen 4 (CD4), the T lymphocyte antigen receptor component and human immunodeficiency virus coreceptor, is down-modulated when cells are activated by antigen or phorbol esters. During down-modulation CD4 dissociates from p56(lck), undergoes endocytosis through clathrin-coated pits, and is then sorted in early endosomes to late endocytic organelles where it is degraded. Previous studies have suggested that phosphorylation and a dileucine sequence are required for down-modulation. Using transfected HeLa cells, in which CD4 endocytosis can be studied in the absence of p56(lck), we show that the dileucine sequence in the cytoplasmic domain is essential for clathrin-mediated CD4 endocytosis. However, this sequence is only functional as an endocytosis signal when neighboring serine residues are phosphorylated. Phosphoserine is required for rapid endocytosis because CD4 molecules in which the cytoplasmic domain serine residues are substituted with glutamic acid residues are not internalized efficiently. Using surface plasmon resonance, we show that CD4 peptides containing the dileucine sequence bind weakly to clathrin adaptor protein complexes 2 and 1. The affinity of this interaction is increased 350- to 700-fold when the peptides also contain phosphoserine residues.

Keywords: JOURNAL ARTICLE Amino Acid Sequence Antigens, CD4/DRUG EFFECTS/GENETICS/*METABOLISM Cytoplasm/METABOLISM Dipeptides/METABOLISM Down-Regulation (Physiology) Endocytosis/DRUG EFFECTS/*PHYSIOLOGY Glutamic Acid/METABOLISM Hela Cells/DRUG EFFECTS/METABOLISM Human Membrane Proteins/*METABOLISM Molecular Sequence Data Peptide Fragments/METABOLISM Phorbol Esters/PHARMACOLOGY Phosphorylation Serine/*METABOLISM *Signal Transduction Support, Non-U.S. Gov't Surface Plasmon Resonance
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