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

被引:138
作者
Pitcher, C
Höning, S
Fingerhut, A
Bowers, K
Marsh, M
机构
[1] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England
[2] UCL, Dept Biochem, London WC1E 6BT, England
[3] Univ Gottingen, D-37073 Gottingen, Germany
关键词
D O I
10.1091/mbc.10.3.677
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:677 / 691
页数:15
相关论文
共 53 条
[1]  
BARZVI D, 1988, J BIOL CHEM, V263, P4408
[2]  
BREMNES B, 1994, J CELL SCI, V107, P2021
[3]   A region from the medium chain adaptor subunit (μ) recognizes leucine- and tyrosine-based sorting signals [J].
Bremnes, T ;
Lauvrak, V ;
Lindqvist, B ;
Bakke, O .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (15) :8638-8645
[4]   A DOUBLE LEUCINE WITHIN THE GLUT4 GLUCOSE-TRANSPORTER COOH-TERMINAL DOMAIN FUNCTIONS AS AN ENDOCYTOSIS SIGNAL [J].
CORVERA, S ;
CHAWLA, A ;
CHAKRABARTI, R ;
JOLY, M ;
BUXTON, J ;
CZECH, MP .
JOURNAL OF CELL BIOLOGY, 1994, 126 (04) :979-989
[5]   Acidic di-leucine motif essential for AP-3-dependent sorting and restriction of the functional specificity of the Vam3p vacuolar t-SNARE [J].
Darsow, T ;
Burd, CG ;
Emr, SD .
JOURNAL OF CELL BIOLOGY, 1998, 142 (04) :913-922
[6]   CD3-GAMMA CONTAINS A PHOSPHOSERINE-DEPENDENT DI-LEUCINE MOTIF INVOLVED IN DOWN-REGULATION OF THE T-CELL RECEPTOR [J].
DIETRICH, J ;
HOU, XH ;
WEGENER, AMK ;
GEISLER, C .
EMBO JOURNAL, 1994, 13 (09) :2156-2166
[7]   Regulation and function of the CD3 gamma DxxxLL motif: A binding site for adaptor protein-1 and adaptor protein-2 in vitro [J].
Dietrich, J ;
Kastrup, J ;
Nielsen, BL ;
Odum, N ;
Geisler, C .
JOURNAL OF CELL BIOLOGY, 1997, 138 (02) :271-281
[8]   CD4-independent infection by HIV-2 is mediated by Fusin/CXCR4 [J].
Endres, MJ ;
Clapham, PR ;
Marsh, M ;
Ahuja, M ;
Turner, JD ;
McKnight, A ;
Thomas, JF ;
StoebenauHaggarty, B ;
Choe, S ;
Vance, PJ ;
Wells, TNC ;
Power, CA ;
Sutterwala, SS ;
Doms, RW ;
Landau, NR ;
Hoxie, JA .
CELL, 1996, 87 (04) :745-756
[9]   Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization [J].
Ferguson, SSG ;
Downey, WE ;
Colapietro, AM ;
Barak, LS ;
Menard, L ;
Caron, MG .
SCIENCE, 1996, 271 (5247) :363-366
[10]   G-protein-coupled receptor regulation: Role of G-protein-coupled receptor kinases and arrestins [J].
Ferguson, SSG ;
Barak, LS ;
Zhang, J ;
Caron, MG .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1996, 74 (10) :1095-1110