Disruption of the CD4-p56lck complex is required for rapid internalization of CD4.
CD4 is a cell surface glycoprotein expressed by a subset of T lymphocytes and functions to enhance T-cell activation. CD4 is noncovalently associated via the cytoplasmic domain with the protein-tyrosine kinase p56lck, a member of the src protein-tyrosine kinase family. Upon activation of protein kinase C by phorbol ester, CD4 is phosphorylated on cytoplasmic serine residues and internalized from the cell surface, and disruption of the CD4-p56lck complex occurs. The exact relationship between these events is likely to be functionally significant, as cytoplasmic-domain serine phosphorylation and internalization have been shown to regulate the function of receptors that possess intrinsic protein-tyrosine kinase activity. Here we demonstrate that p56lck slows the rate of phorbol 12-myristate 13-acetate-induced internalization of CD4 in a manner that depends on a physical association between p56lck and CD4. This decreased rate is due at least in part to a requirement for disruption of the CD4-p56lck complex prior to internalization of CD4. Furthermore, disruption of the CD4-p56lck complex appears to depend on the integrity of the cytoplasmic-domain serine at position 408, probably due to a requirement for phosphorylation.
Sleckman
B P
BP
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Ma.
Shin
J
J
Igras
V E
VE
Collins
T L
TL
Strominger
J L
JL
Burakoff
S J
SJ
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008214:Lymphocytes / Q000201:enzymology; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D015704:CD4 Antigens; D016827:CD8 Antigens; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D013755:Tetradecanoylphorbol Acetate